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The Mo adsorption/99mTc elution properties of alumina used as Mo adsorbents are examined for the development of 99Mo/99mTc generators using 99Mo produced by the (n, γ) method. MoO3 is irradiated by the Kyoto University Research Reactor (KUR). The alumina columns are filled with three types of alumina made from different raw materials. In this paper, elongated tubes are used as columns and the properties under Mo dynamic adsorption conditions on alumina are compared with those under static adsorption conditions. The results obtained suggest that the 99Mo/99mTc ratio specified by the Minimum Requirements for Radiopharmaceuticals of Japan (MRRP) is greatly affected by the method of adsorbing Mo on alumina.

A gated photomultiplier tube (PMT) assembled with an LaBr 3 (Ce) detector was applied toward the prompt γ {\hbox-} ray measurement of fast neutron capture reactions. Time-of-flight measurements of the neutron capture reactions of Cl and Al were performed using the 46-MeV electron linear accelerator at the Kyoto University Research Reactor Institute (KURRI) as a pulsed neutron source. The photomultiplier gating technique effectively suppressed the saturation of the PMT output and extended the energy region of the TOF measurement.

The cross-section of the 237Np reaction has been measured in the energy range from 10 meV to 1 keV using the ANNRI-NaI(Tl) spectrometer at the Japan Proton Accelerator Research Complex (J-PARC). The cross-section was obtained relative to that of the 10B reaction. The absolute value of the cross-section was deduced by normalizing the relative cross-section to the evaluated value of JENDL-4.0 at the first resonance. The thermal cross-section was obtained to be ( ) b. The Maxwellian-averaged cross-section for meV was derived as ( ) b by referring the cross-section below 10 meV from JENDL-4.0. These results lead to the Westcott's g-factor of .

The neutron neutron-capture cross cross-sections of 244Cm and 246Cm were measured by the time-of-flight method in the energy range of 1–300 300 eV with an array of large germanium detectors in the Accurate Neutron-Nucleus Reaction measurement InstrumentANNRI at Material and Life Science Experimental Facility (MLF) of the Japan Proton Accelerator Research ComplexJ-PARC/MLF. The 244Cm resonances at around 7.7 and 16.8 8 eV and the 246Cm resonances at around 4.3 and 15.3 3 eV were observed in the capture reactions for the first time. The uncertainties of the obtained cross cross-sections are 5.8% at the top of the first resonance of 244Cm and 6.6% at that of 246Cm. The rResonance analyses were performed for low-energy ones using the code SAMMY. The prompt γ-ray spectra of 244Cm and 246Cm were also obtained. Eight and five new prompt γ-ray emissions were observed in the 244Cm(n, γ) and 246Cm(n, γ) reactions, respectively.

Measurement of Neutron Capture Cross Section Ratios of Cm Resonances Using NNRI Shinji GOKO a , Atsushi KIMURA a , Hideo HARADA a , Masumi OSHIMA a , Masayuki OHTA a , Kazuyoshi FURUTAKA a , Tadahiro KIN a , Fumito KITATANI a , Mitsuo KOIZUMI a , Shoji NAKAMURA a , Yosuke TOH a , Masayuki IGASHIRA b , Tatsuya KATABUCHI b , Motoharu MIZUMOTO c , Yoshiaki KIYANAGI c , Koichi KINO c , Michihiro FURUSAKA c , Fujio HIRAGA c , Takashi KAMIYAMA d , Jun-ichi HORI d , Toshiyuki FUJJI d , Satoshi FUKUTANI d & Koichi TAKAMIYA a a Nuclear Science and Engineering Directorate , Japan Atomic Energy Agency , Tokaimura, Naka-gun, Ibaraki , 319-1195 , Japan b Research Laboratory for Nuclear Reactors , Tokyo Institute of Technology , O-okayama, Meguro-ku, Tokyo , 152-8550 , Japan c Faculty of Engineering , Hokkaido University , Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido , 060-8628 , Japan d Research Reactor Institute , Kyoto University , Asashiro Nishi, Kumatori-cho, Sennangun, Osaka , 590-0494 , Japan Published online: 05 Jan 2012.

A multi-layered parallel plate ionization chamber (MLPPIC) has been developed for the measurement of neutron-induced fission cross-sections using the lead slowing-down neutron spectrometer at the Research Reactor Institute, Kyoto University. The MLPPIC consists of two sets of multi-layered electrodes to detect fission fragments from two samples located back-to-back between them. The performance of the MLPPIC was tested with a spontaneous fission of 248 Cm. The cross-section for the neutron-induced fission of 241 Am was successfully obtained using that of 235 U as a reference.

Nuclear waste contains a significant amount of long-lived non-gamma-emitting nuclei such as 129 I and 14 C. A method of nondestructive detection for monitoring long-lived waste products is proposed as an application of the (y, n) reaction. This method is useful for surveying long-lived "difficult-to-measure" nuclides, e.g., 129 I. Iodine-128 produced from the reaction of 129 I(γ, n) 128 I emits gamma rays that can easily be measured by a gamma-ray counter. We measured the inclusive photonuclear 129 I(γ, n) 128 I reaction cross section induced by bremsstrahlung photons. The photons were produced at a Ta target bombarded by 30-MeV electrons from a linear accelerator. The intensity of the slow neutrons was considered in the reactions of 127 I(n, γ) 128 I and 129 I(n, γ) 13 °1. The activity of 128 I was measured by a high-purity germanium spectrometer. The gamma-ray flux and the neutron flux were calculated using the EGS and MCNP codes, respectively. The average activation cross section of the 129 I(γ, n ) 128 I reaction had a 12% deviation from the evaluated International Atomic Energy Agency photonuclear data.

We report the transport and thermodynamic properties under hydrostatic pressure in the antiferromagnetic Kondo compound CeMg2Cu9 with a two-dimensional arrangement of Ce atoms. Magnetic specific heat Cmag(T) shows a Schottky-type anomaly around 30 K originating from the crystal electric field (CEF) splitting of the 4f state with the first excited level at \Delta_{1}/kB = 58 K and the second excited level at \Delta_{2}/kB = 136 K from the ground state. Electric resistivity shows a two-peaks structure due to the Kondo effect on each CEF level around T_{1}^{max} = 3 K and T_{2}^{max} = 40 K. These peaks merge around 1.9 GPa with compression. With increasing pressure, Neel temperature TN initially increases and then change to decrease. TN finally disappears at the quantum critical point Pc = 2.4 GPa., Comment: 10 pages, 6 figures

A new data acquisition system (DAQ system) has been developed at the Accurate Neutron-Nucleus Reaction Measurement Instrument (ANNRI) facility in the Japan Proton Accelerator Research Complex, Materials and Life Science Experimental Facility (J-PARC/MLF). DAQ systems for both the Ge detector system and the Li-glass detector system were tested by using a gold sample. The applicability of the time-of-flight method was checked. System performance was evaluated on the basis of digital conversion nonlinearity, energy resolution, multi-channel coincidence and dead time.

To evaluate the feasibility of development of nuclear transmutation technology and an advanced nuclear system, precise nuclear data of neutron capture cross sections for long-lived fission products (LLFPs) and minor actinides (MAs) are indispensable. In this chapter, we present our research activities for the measurements of neutron capture cross sections for LLFPs and MAs.

Neutron resonance capture γ -ray measurements on 74 Se and 77 Se were performed with a 4 π Ge spectrometer in the Accurate Neutron–Nucleus Reaction measurement Instrument (ANNRI) at the Japan Proton Accelerator Research Complex (J-PARC). The relative intensities of primary transitions were derived for the 27-eV resonance of 74 Se and the 113-, 212-, 291-, 342-, 690- and 864-eV resonances of 77 Se, respectively. For the 27-eV resonance of 74 Se, a strong transition to the 293-keV state was observed. Moreover, new resonances of 74 Se were found at 6, 123, 436 and 640 eV. It was confirmed that those resonances had originated in the neutron capture reaction of 74 Se by obtaining the TOF spectrum corresponding to the strong 287-keV ground-state transition γ ray. As for 77 Se, differences of the decay pattern were found between the resonances.

The superconducting transition was investigated in under-doped La2−xSrxCuO4 (LSCO) single crystals under anisotropic pressure. With decreasing x, the transition temperature Tc was found to drop discontinuously from a finite value to zero around xc≈0.05 in the tetragonal lattice of LSCO, while Tc is well known to decrease continuously and to disappear at x≈0.06 in the orthorhombic phase at ambient pressure. The phase change of the tetragonal LSCO across xc looks like a first-order transition as the electron-doped tetragonal Nd2−xCexCuO4 shows in the vicinity of x=0.14. In LSCO doped just above xc, the superconductor–insulator transition is also expected in a single sample by compressing along the c-axis. The transition between the superconducting phase and the magnetic insulating phase is closely related to the in-plane resistivity or the two-dimensional character of electronic state.

To determine whether preservation of the donor cornea prevents allograft rejection, orthotopic corneal transplantation was performed using corneas preserved in storage medium (Optisol-GS((R))). Donor corneas harvested from C3H/He (H-2(k)) mice and B10.D2 (H-2(d)) mice were preserved in storage medium for 0, 3, 7 and 14 days, and then transplanted into the corneal beds of the recipient BALB/c (H-2(d)) mice. Graft survival was determined clinically and histologically. The expression of major histocompatibility complex (MHC) molecules in the preserved corneas was analysed by immunohistochemistry and Western blotting. Donor-specific cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses were assessed 3 weeks after grafting. Active suppression of DTH in the recipient mice was also examined 3 weeks after grafting. The survival of 14 day preserved allografts was significantly higher than that of the non-preserved allografts in both MHC and minor histocompatibility (H) antigens, and minor H only disparate combination. The recipients of the preserved allografts failed to induce both CTL and DTH. The active suppression of DTH was not acquired in these recipients. The expression of donor-derived MHC class I antigens was markedly reduced in the corneas after preservation. Preservation of the donor cornea had a remarkable effect on the prevention of corneal allograft rejection. Since the preserved allografts failed to induce donor-specific CTL and DTH, and active suppression of DTH was not acquired in the recipients, the prevention of allo-rejection is due to a failure of allo-sensitization. These results indicate that the reduction of MHC class I antigens and minor H antigens expression in the preserved grafts induces a failure of allo-sensitization and leads to the high rate of acceptance in corneal allografts.

It has been reported that allograft rejection is mediated by a variety of adhesion molecules. Using a corneal allograft model in mice, we studied the role of very late antigen (VLA)-4 and leukocyte function-associated antigen (LFA)-1 adhesion molecules in corneal allograft rejection and the effects of monoclonal antibodies (mAbs) to them in suppressing corneal rejection. C3H/He donor corneas were transplanted into BALB/c corneal beds. The allografted mice were treated with a control mAb (M18/2), mAbs to VLA-4, or LFA-1 or their combination by i.p. injection until day 7. The expression of VLA-4, LFA-1, major histocompatibility complex (MHC) class II antigens, interleukin (IL)-2, IL-2 receptor and interferon gamma (IFNgamma) in the grafted cornea were studied immunohistochemically. Cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. The skins from a syngeneic donor or a third-part strain were transplanted 8 weeks after the initial keratoplasty onto the mice treated with anti-LFA-1 plus anti-VLA-4 mAbs. Fourteen of 16 allografts in non-treated mice and control mAb-treated mice became opaque by 2 weeks after transplantation. At 2 weeks, non-treated allografts showed expression of MHC class II antigens on keratocytes and mononuclear cells at the host-graft junction. Also, mononuclear cells expressing VLA-4, LFA-1, IL-2, IL-2 receptor and IFNgammawere present in the stroma at the host-graft junction. The allografts treated with either anti-VLA-4 or anti-LFA-1 alone, or anti-VLA-4 plus anti-LFA-1 remained transparent for more than 2 weeks, and the survival rates at 14 weeks was 0%, 16.7%, and 75.0%, respectively. The combined use of anti-VLA-4 and anti-LFA-1 mAbs prolonged graft survival significantly (P

The ACTF installed in the 71-MW PFBC demonstration plant at Wakamatsu Power Station of Electric Power Development Co., Ltd (EPDC) is the first demonstration scale ceramic filter system for high-tem...

The out-of-plane resistivity ( ρ c ) has been measured in under-doped La 2− x Sr x CuO 4 under pressure to investigate the nature of the superconducting transition. The antiferromagnetic insulating sample with x =0.020 did not show superconductivity even under pressure. However, in the non-superconducting samples with x =0.035 and 0.045, an appreciable but incomplete drop of ρ c was observed with lowering temperature and increasing pressure. The drop of ρ c under pressure suggests the existence of the intrinsic phase separation or inhomogeneity around x ∼0.05.

Detailed plasma-physics investigations by the use of x-ray-tomography data supported by the fundamental theoretical studies of x-ray-detector responses enhance the importance of x-ray diagnostics for fusion-plasma analyses. However, degradation in responses of semiconductor x-ray detectors after fusion-produced neutron exposure still remains one of the most serious problems in recent fusion experiments even at this time. For the purpose of investigating and characterizing neutron effects on semiconductor x-ray detectors, detection characteristics of n-type silicon semiconductor detectors which are similar to those utilized for x-ray-tomography detectors in the Joint European Torus (JET) tokamak, are studied by the use of synchrotron radiation from a 2.5-GeV positron storage ring at the Photon Factory. The fusion neutronics source (FNS) of Japan Atomic Energy Research Institute is employed as well-calibrated deuterium-tritium (D-T) neutron source with fluences from 10 13 to 10 15 neutrons/cm 2 onto these semiconductor detectors. Degradation in x-ray responses with increasing neutron fluences has been reported; however, our recent detailed investigations of detector responses show nonlinear dependence as a function of the neutron fluence.

In order to identify the endogenous protease associated with stratum corneum (SC) desquamation, we examined properties of proteases in the stratum corneum of normal human skin. SC were obtained by tape stripping, washed in toluene and then dried. The proteolytic activity in SC was measured using peptidyl 4-methyl-coumaryl-7-amides (MCAs). The SC was dispersed uniformly in the reaction mixture with dimethylformamide and Triton X-100 and incubated with the peptidyl MCAs. The protease in the SC hydrolysed both Boc-Phe-Ser-Arg-MCA and Boc-Gln-Ala-Arg-MCA (substrates for trypsin) very effectively. The hydrolytic activity was inhibited by the serine protease inhibitors diisopropyl fluorophosphate (DFP), aprotinin, antipain and leupeptin, but not by chymostatin, a chymotrypsin inhibitor. These results show that one or more trypsin-like serine protease is present in the SC of normal human skin. Casein-acrylamide electrophoresis showed that the molecular weight of this serine protease was about 30 kDa. We have previously shown that cells dissociate from human SC sheets in a detergent mixture (N,N-dimethyldodecylamine oxide and sodium lauryl sulphate). This cell dissociation was inhibited by aprotinin and leupeptin. In addition, the proteolytic activity in the outer SC was higher than that in the inner SC, and the activity in the SC of scaly skin induced by SLS treatment was higher than that of untreated skin. These results strongly suggest that the trypsin-like serine protease described here is involved in SC desquamation.

Stratum corneum sphingolipids are of particular importance in maintaining the water permeability barrier of mammalian epidermis. Free amino acids also play an important role in water retention in the stratum corneum. To clarify the way in which these substances affect scaly skin, stratum corneum sphingolipids and free amino acids collected from artificially-induced scaly skin were analysed. Scaly skin was induced by tape stripping. The total amount of sphingolipids was quantified by gas chromatography and five of sphingolipid fractions were isolated and quantified by thin-layer chromatography. Free amino acids were analysed using a high-speed amino analyser. The total amount of sphingolipid in scaly skin did not differ statistically from that in control skin. However, a significant change in the distribution of the five sphingolipid species was observed in scaly skin and the total amount of amino acids was decreased in scaly skin. These results suggest that the distribution of these five types of sphingolipid and the total amount of amino acids are responsible for scaly skin.

A horizontal and vertical dipole layer model was developed for three dimensional dipole layer imaging of brain electrical activity. Horizontal dipole layer being parallel to the brain surface has been used in previous head models. In the present study, the dipole layer distribution in the sagittal plane was also estimated from the scalp electroencephalogram. The parametric projection filter was applied to an inverse problem in a homogeneous plane head model under various signal conditions. The present simulation results suggest that the depth information of dipole sources could be observed by our method.

The objective of this study is to explore suitable spatial filters for inverse estimation of cortical equivalent dipole layer imaging from the scalp electroencephalogram. We utilize cortical dipole source imaging to locate the possible generators of scalp-measured movement-related potentials (MRPs) in human.The effects of incorporating signal and noise covariance into inverse procedures were examined by computer simulations and experimental study. The parametric projection filter (PPF) and parametric Weiner filter (PWF) were applied to an inhomogeneous three-sphere head model under various noise conditions.The present simulation results suggest that the PWF incorporating signal information provides better cortical dipole layer imaging results than the PPF and Tikhonov regularization under the condition of moderate and high correlation between signal and noise distributions. On the other hand, the PPF has better performance than other inverse filters under the condition of low correlation between signal and noise distributions. The proposed methods were applied to self-paced MRPs in order to identify the anatomic substrate locations of neural generators. The dipole layer distributions estimated by means of PPF are well-localized as compared with blurred scalp potential maps and dipole layer distribution estimated by Tikhonov regularization. The proposed methods demonstrated that the contralateral premotor cortex was preponderantly activated in relation to movement performance.In cortical dipole source imaging, the PWF has better performance especially when the correlation between the signal and noise is high. The proposed inverse method was applicable to human experiments of MRPs if the signal and noise covariances were obtained.

Neutron capture cross sections of minor actinides and long-lived fission products are important for the R&D of innovative nuclear reactors. However, those data are rather poor both in quality and in quantity at present. Thus, we have started projects for neutron cross section measurements. We have constructed an 4π Ge spectrometer consisting of Ge crystals and BGO shields. The neutron cross section measurements have been done at KURRI electron linac and JAEA JRR-3 facilities, which will be extended at the high-intensity neutron source at J-PARC.

The neutron capture cross section of natural palladium has been measured relative to 10B(n,α) standard cross section by the neutron time‐of‐flght (TOF) method in the energy range of 0.01 eV to 10 keV using a detection assembly of Bi4Ge3O12 (BGO) scintillators and a 46 MeV electron linear accelerator (linac) at the Research Reactor Institute, Kyoto University (KURRI). The relative cross section has been normalized at 0.0253 eV to the reference value estimated by using the cross sections of stable palladium isotopes in the JENDL‐3.3 library. The present results were compared with the evaluated values in the JENDL‐3.3.

A distortion of pulse‐height spectra of neutron capture γ‐rays caused by γ‐flash at neutron time‐of‐flight (TOF) measurement using a pulse neutron source has been investigated. Pulses from C6D6 detectors accumulated by flash‐ADC were processed with both traditional analog‐to‐digital converter (ADC) and flash‐ADC operational modes. A correction factor of γ‐ray yields, due to baseline shift, was quantitatively obtained by comparing the pulse‐height spectra of the two data‐collecting modes. The magnitude of the correction factor depends on the time, which passed after γ‐flash, and has complicated time dependence with a changing sign.

The specific heat (C) of the chalcogenide compound superconductor TlV6S8 has been measured by the thermal relaxation method. The superconducting transition temperature (Tc) obtained from the C was ∼ 2.5 K. The Sommerfeld coefficient γ estimated from the C in the normal state was 163 mJ / K2 mol. γ of TlV6S8 is fairly large compared to that of the conventional superconductors. The large value of γ indicates that TlV6S8 is one of the strongly correlated electron systems. The value of C/T below Tc increased gradually with decreasing temperature and had a peak at ∼ 2 K. We suspect that this behavior is derived from the quasi‐one‐dimensional structure.

Hard x-ray photoemission spectroscopy (PES) of Cu core electronic states, with a probing depth of approximately 60 A, is used to show that the Zhang-Rice singlet feature is present in La2CuO4 but is absent in Nd2CuO4. Hole and electron doping in La(2-x)SrxCuO4 (LSCO) and Nd(2-x)CexCuO4 (NCCO) result in new well-screened features which are missing in soft x-ray PES. Impurity Anderson model calculations establish screening from doped states as its origin, which is strongly suppressed within 15 A of the surface. Complemented with x-ray absorption spectroscopy, the small chemical-potential shift in core levels (approximately 0.2 eV) are shown to be consistent with modifications of valence and conduction band states spanning the band gap (approximately 1 eV) upon hole and electron doping in LSCO and NCCO.

We performed resistivity measurements in CuRh2S4 under quasihydrostatic pressure of up to 8.0 GPa, and found a pressure-induced superconductor-insulator transition. Initially, with increasing pressure, the superconducting transition temperature T(c) increases from 4.7 K at ambient pressure to 6.4 K at 4.0 GPa, but decreases at higher pressures. With further compression, superconductivity in CuRh2S4 disappears abruptly at a critical pressure P(SI) between 5.0 and 5.6 GPa, when it becomes an insulator.

We performed resistivity measurements in CuRh2S4 under quasihydrostatic pressure of up to 8.0 GPa, and found a pressure-induced superconductor-insulator transition. Initially, with increasing pressure, the superconducting transition temperature T(c) increases from 4.7 K at ambient pressure to 6.4 K at 4.0 GPa, but decreases at higher pressures. With further compression, superconductivity in CuRh2S4 disappears abruptly at a critical pressure P(SI) between 5.0 and 5.6 GPa, when it becomes an insulator.

The purpose of this study was to investigate the role of CD80 and CD86 costimulatory molecules in corneal allograft rejection. Anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) were administered after orthotopic corneal allograft transplantation. Graft rejection was observed by biomicroscopy. Population and localization of CD80 + and CD86 + cells in the cornea, cervical lymph nodes, and spleen were examined by flow cytometry and immunohistochemistry. The combined use of anti-CD80 and anti-CD86 mAbs was effective in prolonging corneal allograft survival. In the untreated mice bearing rejected graft, many CD86 + and CD80 + cells were found around the host-graft junctional area in the cornea, and CD86 high cells were found in the cervical lymph node and spleen. In contrast, few CD86 + or CD80 + cells were observed in the cornea, cervical lymph node, and spleen from the mice treated with anti-CD80/CD86 mAbs. These results demonstrated a significant role of CD80 and CD86 costimulatory molecules in corneal allograft rejection.

We measured six stratum corneum sphingolipid species (ceramides 1-6) in 26 males and 27 females, and found a significant change in their percentage composition only among female subjects of different age groups. There was a significant increase in ceramide 1 and 2 with a corresponding decrease in ceramide 3 and 6 from prepubertal age to adulthood. Thereafter the ratio of ceramide 2 to total sphingolipids decreased with age in contrast to ceramide 3 which showed an increase. Such a pattern of change in the aging population is different from that observed in scaly skin experimentally induced by tape stripping. The present results suggest a significant influence of female hormones on the composition of stratum corneum sphingolipids. Moreover, the different patterns of change in sphingolipid composition of stratum corneum lipids between scales from inflammatory skin and those from aged skin also suggest that epidermal biosynthesis of sphingolipids is influenced by epidermal proliferative activity.

To determine the extent to which donor cells persist and recipient cells repopulate each of the three cell layers of orthotopic corneal grafts in mice.BALB/c, C57BL/6, and enhanced green fluorescence protein (EGFP) transgenic mice (B6 background) were used as donors and recipients for orthotopic syngeneic and allogeneic corneal grafts. Graft-bearing eyes were harvested at 5, 10, 15, 28, and 56 days, stained with propidium iodide, and observed (layer by layer) by confocal microscopy. Bone marrow-derived cells in the grafts were assessed immunohistochemically.Donor epithelium was totally replaced by recipient epithelial cells within 15 days in both syngeneic and allogeneic grafts, whereas donor stromal keratocytes and endothelial cells were retained virtually intact in syngeneic grafts and in accepted allografts. In rejected allografts, neither donor-derived keratocytes nor endothelial cells were detected, and, instead, recipient-derived stromal fibroblasts, neovessels, and infiltrating leukocytes were heavily represented. The posterior surface of rejected grafts was devoid of corneal endothelium and was covered incompletely with bone marrow-derived cells of recipient origin.Whereas in mice graft-derived epithelium is largely irrelevant to corneal allograft outcome, persistence of donor-derived endothelium and keratocytes correlates perfectly with graft acceptance. Recipient endothelium is incapable of covering the posterior surface of accepted or rejected corneal grafts, whereas bone marrow-derived cells of recipient origin come to occupy this site in rejected grafts.

To determine whether epithelium-deprived corneal allografts covered with syngeneic epithelium display immune privilege in orthotopic transplantation and whether syngeneic epithelium containing antigen-presenting cells nullifies this effect.Epithelium-deprived allogeneic corneas (C57BL/6) and epithelium-deprived allogeneic corneas reconstituted with syngeneic (BALB/c) epithelium (containing or deprived of Langerhans' cells) were transplanted orthotopically into normal eyes of BALB/c mice. Graft survival was assessed clinically and evaluated histologically.Epithelium-deprived corneal grafts survived in syngeneic recipients but were swiftly rejected in allogeneic recipients. These allografts incited intense stromal inflammation and neovascularization. Epithelium-deprived allografts that were resurfaced in vivo by syngeneic epithelium derived from immune-incompetent SCID mice also underwent intense acute rejection when placed in normal eyes of BALB/c mice. The epithelium of in vivo resurfaced grafts was replete with Langerhans' cells. By contrast, most of the epithelium-deprived allografts reconstituted in vitro with fresh, normal BALB/c corneal epithelium survived indefinitely when placed in eyes of BALB/c mice. Similar grafts reconstituted with BALB/c epithelium containing Langerhans' cells were swiftly rejected.Replacement of donor epithelium with Langerhans' cell-deficient syngeneic epithelium protects orthotopic allogeneic cornea grafts (stroma plus endothelium) from immune-mediated rejection. The presence of an intact, histocompatible layer of corneal epithelium has two important effects on orthotopic corneal allografts: It suppresses nonspecific inflammation and neovascularization within the graft, and it blunts the alloimmunogenicity of the histoincompatible stroma and endothelium.

To determine the extent to which each layer of the mouse cornea displays alloimmunogenicity or immune privilege.Intact corneas or individual or combined layers of corneas from normal or cauterized eyes of BALB/c, C57BL/6, and CD95L-deficient B6-gld mice were grafted beneath the kidney capsule of normal BALB/c, B10.D2, BALB.B mice or of BALB/c mice presensitized to donor antigens. Graft fate was assessed clinically and histologically and acquisition of donor-specific delayed hypersensitivity (DH) was assessed at selected intervals after grafting.Full-thickness allogeneic corneas induced vigorous DH and were rejected acutely. Similar results were obtained with allografts of corneal epithelium alone (if supported by syngeneic viable stroma), allografts of epithelium from cauterized corneas (containing Langerhans' cells), and stromal allografts deprived of endothelium. Grafts comprised of stroma plus endothelium (without epithelium) were not rejected, nor did they induce DH unless the graft had no CD95L expression. If stroma-endothelium grafts had no CD95L expression, DH directed against major histocompatibility complex (MHC), but not minor histocompatibility, alloantigens was induced. Moreover, CD95L expressed on stroma-endothelium grafts protected endothelial cells, but not stromal cells, from rejection in presensitized recipients.When grafted to a heterotopic site, the alloimmunogenicity of the normal cornea resides within its epithelial and stromal layers, whereas immune privilege arises from the endothelium. In normal mice, CD95L-expressing endothelium can inhibit the stroma from inducing immunity directed at MHC alloantigens, but in presensitized mice the endothelium can protect itself only from immune rejection.

To determine whether corneal tissue as an allograft displays immune privilege in a nonprivileged site and, if so, whether CD95 ligand expression contributes to the privileged status.Syngenic and allogeneic corneal tissues deprived of epithelium were transplanted beneath the kidney capsule of normal mice. Syngeneic BALB/c, allogeneic C57BL/6, and allogeneic B6Smn.C3H-gld (CD95 ligand-deficient) mice were used as donors for BALB/c recipients, and syngeneic C3H/HeJ-gld (CD95 ligand-deficient) mice were used for normal C3H/HeJ recipients. Allogeneic conjunctival segments served as positive grafting controls. Graft fate was assessed by visual inspection at 4, 7, 14, and 21 days and was confirmed by histologic study. Viability of graft endothelium was assessed by immunocytochemical analysis.Syngeneic corneas and C57BL/6 corneas survived almost indefinitely beneath the kidney capsule. Both the stroma and the endothelial layers remained healthy and intact. Allogeneic conjunctiva evoked a strong inflammatory response attended by neovascularization. Similarly, B6-gld corneas deficient in CD95 ligand expression showed acute destruction beneath the kidney capsule. Circumstantial evidence implicates alloimmune rejection as the mechanism.Epithelium-deprived corneas from normal mice possess inherent immune privilege that protects them from alloimmune rejection even at nonprivileged sites. Constitutive expression of CD95 ligand contributes to the privileged status. It is inferred that the extraordinary success of orthotopic corneal allografts owes as much to the qualities of the graft as an immune-privileged tissue as to the qualities of the eye as an immune-privileged site.

Allograft rejection is the expression of an immune reaction of the recipient against foreign antigens of the transplanted tissue and is mostly mediated by T lymphocytes. The initial step consists of T lymphocyte adhesion to graft endothelium, a process that is mediated by cell adhesion molecules. It has been shown that there are several pathways for recognition of alloantigens on the transplanted vascularized organs, and cell adhesion molecules play important roles in these processes. Adhesion is necessary for tightening of contact between T cells and antigen-presenting cells. Two signals are required for optimal clonal expansion of T cells: one from the T cell receptor upon binding to the major histocompatibility complex (MHC) antigen and the other signal from receptors that are distinctive from T cell receptors (Mueller et al. 1989; Schwartz et al. 1989; Schwartz 1990). Shaw et al. found that several adhesion molecules produce such costimulatory signals (Clevers et al. 1988; Shimizu et al. 1990a; Weaver and Unaue 1990). Schwartz et al. showed that, in the absence of the costimulatory signal, T cells become inactivated against the particular antigen, which leads to clonal anergy of the T cells (Mueller et al. 1989).

Corneal transplantation was performed by grafting C3H/He donor corneas into BALB/c corneal beds. The allografted mice were injected either with 0.5 mg/day of anti-very late antigen (VLA)-4 antibody, anti-leukocyte function-associated antigen (LFA)-1 antibody, or 0.25 mg/day each of both antibodies on days -2, 0, 1, 3, 5, and 7. After 3 weeks, cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. Splenocytes in the allografted mice without treatment demonstrated greater CTL responses that those in naive mice. CTL responses were depressed in mice treated with either anti-LFA-1 alone or a combination of anti-LFA-1 and anti-VLA-4 antibodies as compared with splenocytes from allografted mice without treatment. These data suggest that CTLs play significant roles in eliciting immune response to corneal allografts.