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Proliferation of latently infected [CD4.sup.+] T cells with replication- competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating [CD4.sup.+] memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA-treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of [CD4.sup.+] TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir., Introduction The advent of antiretroviral therapy (ART) has dramatically improved the life expectancy of people with HIV (PWH) infection. However, current ART regimens act by blocking de novo infection of [...]

Organic dust exposure in agricultural animal environments results in airway diseases. Dendritic cells (DCs) orchestrate inflammatory immune response in the airways, but little is known about how organic dust affects differentiation and maturation of monocyte-derived immature and mature DCs (iDCs, mDCs). Peripheral blood monocytes were differentiated in vitro into iDCs with granulocyte-macrophage colony stimulating factor + IL-4 (6 days) with and without swine facility organic dust extract (ODE, 0.1%). Unlike control iDCs, ODE-conditioned iDCs maintained key monocyte properties (increased mCD14, increased phagocytic ability) while expressing DC features [increased mCD83, HLA-DR, CD80, CD86, diminished cytokine (TNF-[alpha], IL-6) responsiveness]. At day 6, iDCs were cultured for an additional 48 h (days 7 and 8) with lipopolysaccharide (LPS) to induce mDCs. ODE-conditioned mDCs maintained high expression of [mCD14.sup.+] and elevated phagocytosis while their DC features weakened as evidenced by decreased CD11c, CD83, HLA-DR, CD86, and CCR7 expression and reduced lymphocyte-stimulating capacity. Similar results were observed when monocytes were exposed to ODE for only the first 48 h and with ODE depleted of endotoxin. Control iDCs exposed to ODE during the final 2 days of iDC maturation (days 7 and 8) did not differ from control (no ODE) iDCs in surface marker expression and phagocytic ability, but exhibited enhanced lymphocyte-stimulating capacity. Dust exposure alters monocyte differentiation to iDCs and prevents maturation of iDC to mDCs. The first 48 h of monocyte differentiation appears to be the susceptible period to exposure. Environmental exposures present during early monocyte differentiation may impact the critical balance of DCs in the lung. phagocytosis; lymphocyte proliferation; innate cell surface molecules; cytokines; swine doi: 10.1152/ajplung.00107.2009

CD1 proteins constitute a distinct lineage of antigen-presenting molecules specialized for the presentation of lipid antigens to T cells. In contrast to the extensive sequence polymorphism characteristic of classical MHC molecules, CD1 proteins exhibit limited sequence diversity. Here, we describe the identification and characterization of CD1d alleles in wild-derived mouse strains. We demonstrate that polymorphisms in CD1d affect the presentation of endogenous and exogenous ligands to CD1d-restricted T cells, including type I (V[alpha]14i) and type II (non-V[alpha]14i) natural killer T (NKT) cells. Using congenic mice, we found CD1d polymorphisms affect the thymic selection of type I NKT cells and induce allogeneic T cell responses. Collectively, results from these studies demonstrate a role for polymorphisms in influencing the development and function of CD1d-restricted T cells. T cell activation | T cell development

A small fraction of the CD8 T cell effector population that responds to an infection progresses through the contraction phase to the memory stage. The factors regulating the extent of contraction are poorly understood. Competition for limited resources has been widely postulated to be the cause of cell death during the contraction phase, but our data show that competition does not affect contraction kinetics. We go on to demonstrate that all effector cells present at the peak of the response have the potential to become bona fide memory cells, thus excluding selection on the basis of functionality. We propose that the fate of a CD8 effector cell is predetermined before the onset of contraction and discuss possible mechanisms of regulation. infection | Listeria monocytogenes | memory | effector | bim

Mechanisms by which the extracellular domain of Notch1 controls Notch1 signaling are not well defined. Here, we show that the O-fucose glycan in the Notch1 ligand-binding domain regulates the strength of Notch1 signaling during embryogenesis, postweaning growth, and T cell development in the mouse. Heterozygotes carrying a Notch[1.sup.12f] allele and an inactive Notch1 allele die at approximately embryonic day (E)12 with a typical Notch1 null phenotype. Homozygous Notch[1.sup.12f/12f] mice are viable and fertile but grow somewhat more slowly than littermates after weaning. Notch[1.sup.12f/12f] thymocytes bind less Delta1 and exhibit reduced Notch1 signaling. The number of double-positive (DP) and singlepositive (SP) T cells are decreased in Notch[1.sup.12f/12f] thymus, and DP T cells are more apoptotic. By contrast, proportionately more SP cells have matured, and SP-to-DP ratios are increased in mutant thymus. Thus, the O-fucose glycan in EGF12 of mouse Notch1 is required for optimal Notch1 signaling and T cell development in mammals. hypomorphic mutation | Notch signaling | O-fucosylation mutant

T cell Ig mucin 1 (TIM-1) plays an important role in regulating immune responses in autoimmune and asthma models, and it is expressed on both Th1 and Th2 cells. Using an antagonistic TIM-1-specific antibody, we studied the role of TIM-1 in alloimmunity. A short course of TIM-1-specific antibody monotherapy prolonged survival of fully MHC-mismatched vascularized mouse cardiac allografts. This prolongation was associated with inhibition of alloreactive Th1 responses and preservation of Th2 responses. TIM-1-specific antibody treatment was more effective in Th1-type cytokine--deficient Stat4-/- recipients as compared with Th2-type cytokine--deficient Stat6-/- recipients. Subtherapeutic doses of rapamycin plus TIM-1-specific antibody resulted in allograft acceptance and prevented the development of chronic allograft vasculopathy. Allograft survival via this treatment was accompanied by a Th1- to Th2-type cytokine switch. Depletion of natural Tregs abrogated the graft-protecting effect of the TIM-1-specific antibody. Importantly, [CD4.sup.+][CD25.sup.+] Tregs obtained from long-term survivors had enhanced regulatory activity as compared with naive [CD4.sup.+][CD25.sup.+] Tregs. Consistent with this, TIM-1-specific antibody treatment both preserved Tregs and prevented the expansion of alloreactive effector Th1 cells in an alloreactive TCR transgenic adoptive transfer model. These studies define previously unknown functions of TIM-1 in regulating alloimmune responses in vivo and may provide a novel approach to promoting transplantation tolerance., Introduction The T cell Ig mucin (TIM) family of genes encodes proteins that are expressed by T cells and contain an IgV-like and a mucin-like domain (1). The TIM family [...]

Regulatory T cells ([T.sub.reg]) migrate into allografts and induce tolerance of the graft. Immunosuppressive Treg are found among CD[4.sup.+]CD[25.sup.++] T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and Treg might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD[4.sup.+]CD[25.sup.++] [T.sub.reg] in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients (n = 22) compared with controls (n = 18). Systemic levels of circulating Treg were significantly lower in CA recipients (8.9 [+ or -] 1.3 [micro]l) compared with controls (15.8 [+ or -] 1.6 [micro]l; P = 0.002). Similarly, the proportion of [T.sub.reg] related to the total leukocyte number was significantly lower in CA recipients (P < 0.01). In contrast, systemic levels of circulating activated CD[4.sup.+] T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of Treg significantly decreased during transcardiac passage (3.0 [+ or -] 0.3 to 2.4 [+ or -] 0.3% of CD[4.sup.+] T cells, P < 0.01), and FOXP[3.sup.+] T cells invaded into the allograft. In contrast, numbers of activated CD[4.sup.+] T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive [T.sub.reg] are reduced in transplant recipients. Recruitment of [T.sub.reg] into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy. coronary circulation; chronic inflammation doi: 10.1152/ajpheart.01197.2006.

In contrast to naive [CD4.sup.+] T cells, memory [CD4.sup.+] T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes. Here we show that memory [CD4.sup.+] T cells rapidly induce NFAT-mediated transcription upon T cell receptor ligation whereas NFAT activation in naive [CD4.sup.+] T cells requires longer periods of stimulation. The difference in kinetics correlates with the low levels of NFATcl and NFATc2 proteins present in naive [CD4.sup.+] T cells and their high levels in memory [CD4.sup.+] T cells. Accordingly, IL-2 expression requires NFAT activation only in memory [CD4.sup.+] T cells whereas it is NFAT-independent in naive [CD4.sup.+] T cells. Thus, the accumulation of NFATc1 and NFATc2 in memory [CD4.sup.+] T cells represents a previously uncharacterized regulatory mechanism for the induction of early gene expression after antigen stimulation. T cell activation | regulation of transcription

Although studies with primary lymphocytes are almost always conducted in C[O.sub.2] incubators maintained at atmospheric oxygen levels (atmos[O.sub.2]; 20%), the physiological oxygen levels (phys[O.sub.2]; 5%) that cells encounter in vivo are 2-4 times lower. We show here that culturing primary T cells at atmos[O.sub.2] significantly alters the intracellular redox state (decreases intracellular glutathione, increases oxidized intracellular glutathione), whereas culturing at phys[O.sub.2] maintains the intracellular redox environment (intracellular glutathione/oxidized intracellular glutathione) close to its in vivo status. Furthermore, we show that CD3/CD28-induced T cell proliferation (based on proliferation index and cell yield) is higher at atmos[O.sub.2] than at phys[O.sub.2]. This apparently paradoxical finding, we suggest, may be explained by two additional findings with CD3/CD28-stimulated T cells: (i) the intracellular NO (iNO) levels are higher at phys[O.sub.2] than at atmos[O.sub.2]; and (ii) the peak expression of CD69 is significantly delayed and more sustained at phys[O.sub.2] that at atmos[O.sub.2]. Because high levels of intracellular NO and sustained CD69 tend to down-regulate T cell responses in vivo, the lower proliferative T cell responses at phys[O.sub.2] likely reflect the in vitro operation of the natural in vivo regulatory mechanisms. Thus, we suggest caution in culturing primary lymphocytes at atmos[O.sub.2] because the requisite adaptation to nonphysiological oxygen levels may seriously skew T cell responses, particularly after several days in culture. glutathione | low oxygen | nitric oxide | proliferation

Activation of the transcription factor NF-[kappa]B after stimulation through antigen receptors is important for lymphocyte differentiation, activation, proliferation, and protection against apoptosis. Much progress has been made in understanding the molecular events leading to NF-[kappa]B activation, but how this activation is eventually down-regulated is less well understood. Recent studies have indicated that Bcl10 functions downstream of lymphocyte antigen receptors to promote the activation of the I[kappa]B kinase complex leading to the phosphorylation and degradation of the I[kappa]B inhibitors of NF-[kappa]B. Bcl10 has also been implicated in the pathogenesis of mucosa-associated lymphoid tissue lymphoma, possibly in association with its nuclear localization. Here, we provide evidence that the I[kappa]B kinase complex phosphorylates Bcl10 after T cell antigen receptor stimulation and causes its proteolysis via the [beta]-TrCP ubiquitin ligase/proteasome pathway. These findings document a negative regulatory activity of the IKK complex and suggest that Bcl10 degradation is part of the regulatory mechanisms that precisely control the response to antigens. Mutants of Bcl10 in the IKK phosphorylation site are resistant to degradation, accumulate in the nucleus, and lead to an increase in IL-2 production after T cell antigen receptor stimulation. NF-kB | ubiquitination | signal transduction

The thymus, the site of origin of T cell immunity, shapes the repertoire of T cell reactivity through positive selection of developing T cells and prevents autoimmunity through negative selection of autoreactive T cells. Previous studies have demonstrated an important role for the thymus not only in central deletional tolerance, but also in the induction of peripheral tolerance by vascularized renal allografts in juvenile miniature swine recipients. The same protocol did not induce tolerance in thymectomized recipients nor in recipients beyond the age of thymic involution. We subsequently reported that vascularized thymic lobe grafts from juvenile donors were capable of inducing tolerance in thymectomized juvenile hosts. However, the important question remained whether aged, involuted thymus could also induce tolerance if transplanted into thymectomized hosts, which, if true, would imply that thymic involution is not an intrinsic property of thymic tissue but is rather determined by host factors extrinsic to the thymus. We report here that aged, involuted thymus transplanted as a vascularized graft into juvenile recipients leads to rejuvenation of both thymic structure and function, suggesting that factors extrinsic to the thymus are capable of restoring juvenile thymic function to aged recipients. We show furthermore that rejuvenated aged thymus has the ability to induce transplant tolerance across class I MHC barriers. These findings indicate that it may be possible to manipulate thymic function in adults to induce transplantation tolerance after the age of thymic involution. aging | miniature swine | thymus

The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and [...]

Aging is often associated with a dysregulation in immune function, particularly in T-cell responses, even in the healthy elderly. Adequate nutrition is important for optimal immune function. The literature on the relation of nutritional status with immune function in the elderly offers mixed findings. Because several nutrients can influence immune response, and there are interactions among nutrients, examining the association of various nutrients measured simultaneously with tests of immune function is important. We examined the association of protein, iron, zinc, vitamin B-12, and folic acid with tests of acquired immunity in healthy older women (76.7 [+ or -] 7.0 y; n = 130). Discriminant analysis was used to identify the predictive subset of nutrients that could correctly classify subjects into the lowest or highest quartiles ([less than or equal to] 25th or >75th percentile) on various immune function tests (T cells and subsets and lymphocyte proliferation in response to culture with mitogens). Protein and iron status variables were identified in the predictive subset for all immune tests; in addition, zinc emerged in the predictive model for T cells and their subsets as well as for the proliferation response to concanavalin A. The probability of correctly classifying women into the lowest or highest quartiles of immune tests by the predictive subset of nutrition variables was high, i.e., 62.8-83.5% for T cells and their subsets, and 79.3-89.7% for the proliferation response to mitogens. In conclusion, protein, iron, and zinc were significant predictors of immune function in older women. Adequate status of these nutrients may help maintain immunity in older adults. KEY WORDS: * immune function * nutrition * leukocyte subsets * lymphocyte proliferation * aging

The molecular basis for the different roles of IL-2 and IL-15 in lymphocyte function has been poorly defined. Searching for differences that underlie the distinct T cell responses to the two cytokines, we observed a marked susceptibility of the IL-15-induced but not of the IL-2-induced proliferation to rapamycin despite a decrease of p70S6 kinase ([p70.sup.s6K]) activation by the drug in response to both cytokines. Activated splenic T lymphocytes deficient in the FK506-binding protein (FKBP) 12, a target of rapamycin activity, had reduced proliferation in response to IL-15 but not to IL-2. This decreased proliferation was accompanied by reduced activation of [p70.sup.s6K] and of the extracellular signal-regulated kinases (ERK) after IL-15 treatment. In contrast to FKBP12-/cells, splenic FKBP12.[6.sup.-/-] T cells exhibited a decreased proliferative response to IL-2 in the presence of rapamycin without affecting [p70.sup.s6K] or ERK activation. Thus, IL-15 induces T cell proliferation mainly via FKBP12-mediated [p70.sup.s6K] activation. In contrast, IL-2 signaling involves multiple pathways that include at least one additional pathway that depends on FKBP12.6.

[CD4.sup.+] T cells expand after transfer into lymphopenic H-[2.sup.b] [A.sub.[beta].sup.-/-] mice (I-[A.sub.[beta]]-, I-[E.sub.[alpha]]-deficient mice) but not after transfer into lymphopenic MHC [II.sup.[DELTA]/[DELTA]] mice (I-[A.sub.[alpha]]-, I-[A.sub.[beta]]-, I-[E.sub.[alpha]]-, and I-[E.sub.[beta]]-deficient mice), implying that in H-[2.sup.b] [A.sub.[beta].sup.-/-] mice, [A.sub.[alpha]] chain and [E.sub.[beta]] chain associate to form a hybrid [A.sub.[alpha]][E.sub.[beta]] MHC class II molecule. In light of this unexpected result, we reexamined the MHC class II requirement in the survival and lymphopenia-induced proliferation of [CD4.sup.+] T cells. Here we show that expansion, but not short-term survival, of [CD4.sup.+] T cells depends on interactions with MHC class II molecules in lymphopenic mice. Nevertheless, interactions with classical MHC class II molecules are required for [CD4.sup.+] T cells to survive in [CD8.sup.+] T-cell-containing mice.

Naive T cells do not proliferate in normal individuals in the absence of antigen stimulation, but they proliferate spontaneously when T cells are severely depleted. We show here that coculture of syngeneic dendritic cells (DC) with naive T cells expressing a single T cell receptor also results in T cell proliferation in the absence of foreign antigen. As in lymphopenic mice, where T cell proliferation depends upon DC, this response in the coculture system requires interaction of the T cells' T cell receptor with self-peptide-MHCs on DC. This in vitro proliferation also requires soluble factors, including IL-15 secreted by DC, and can be inhibited potently by cell-cell contact with [CD4.sup.+] [CD25.sup.+] regulatory T cells. The coculture system described may illuminate mechanisms that maintain stable numbers of T cells in normal individuals.

A study was conducted to describe the mechanisms of pulmonary surfactant protein A (SP-A) as an immune suppressive agent. SP-A was found to inhibit human T lymphocyte proliferation in a dose dependent manner and that the effect is not mediated by the carbohydrate recognition domain of SP-A. Results implied a potential role for SP-A in inhibiting lymphocyte responses to exogenous stimuli, as well as support the hypothesis that SP-A contributes to the inhibition of in vivo T cell proliferation and that the effect helps maintain the hyporesponsive state of pulmonary leukocytes.

Chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 produces CD4+ T-cell clones. These have low proliferative capacity and produce low levels of IL-2, high levels of IL-10 and no IL-4. The antigen-specific T-cell clones inhibit colitis induced in SCID mice by pathogenic CD4+CD45RBhigh splenic T cells. Tr1 cells suppress immune responses directed against other antigens in the microenvironment, and they could therefore possibly be used to control T-cell-mediated disease, even when the identity of the pathogenic antigen has not been established.

T cell proliferation in vivo is presumed to reflect a T cell receptor (TCR)-mediated polyclonal response directed to various environmental antigens. However, the massive proliferation of T cells seen in viral infections is suggestive of a bystander reaction driven by cytokines instead of the TCR. In mice, T cell proliferation in viral infections preferentially affected the [CD44.sup.hi] subset of [CD8.sup.+] cells and was mimicked by injection of polyinosinic-polycytidylic acid [poly(I:C)], an inducer of type I interferon (IFN 1), and also by purified IFN 1; such proliferation was not associated with up-regulation of CD69 or CD25 expression, which implies that TCR signaling was not involved. IFN I [poly(I:C)]-stimulated [CD8.sup.+] cells survived for prolonged periods in vivo and displayed the same phenotype as did long-lived antigen-specific [CD8.sup.+] cells. IFN I also potentiated the clonal expansion and survival of [CD8.sup.+] cells responding to specific antigen. Production of IFN I may thus play an important role in the generation and maintenance of specific memory., Viral infections generally induce vigorous immune responses that culminate in a longlasting state of immune memory. The sharp transient increase in total T cell numbers found in certain viral infections [...]

Immunoblotting and SDS-PAGE studies reveal that the 23 kDa cytosolic protein antigen of the vaccine candidate Mycobacterium habana is superoxide dismutase (SOD). The 18 N-terminal amino acid sequence of the enzyme is similar to those of M. tuberculosis, M. leprae and human SODs. T cells of guinea-pigs and mice primed with M. habana recognize M. habana SOD. The enzyme also induces T lymphocyte proliferative responses similar to those induced by M. leprae in human tuberculoid leprosy patients and individuals exposed to environmental mycobacteria.

The generation of mice with congential deficiency of TcR-alpha-beta-expressing cells helps study the independent in vivo TcR-gamma-delta+ cell activity in the absence of TcR-alpha-beta+ cells. Challenge by environmental antigens leads to enlargement of the lymphoid organs in TcR-alpha mutant mice. The use of multiple gamma and delta variable chain segments indicates polyclonal expansion of the TcR-gamma-delta+ population, with the activation of majority of the cells that express surface activation markers.

A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated. The cytokine, designated interleukin-15 (IL-15), is produced by a wide variety of cells and tissues and shares many biological properties with IL-2. Monoclonal antibodies to the β chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor., The proliferation and differentiation of T lymphocytes is regulated by cytokines that act in combination with signals induced by the engagement of the T cell antigen receptor. A principal cytokine [...]

A study was done on the rapid internalization of CD4, a cell surface glycoprotein expressed by a subset of T lymphocytes. CD4 promotes T-cell activation and is phosphorylated on cytoplasmic serine residues upon stimulation with protein kinase C. This results to the disruption of the CD4-p56lck complex, a process found to be essential in the rapid internalization of CD4.

Herpesvirus saimiri is a common cause of T-cell lymphomas in monkeys and is capable of immortalizing monkey T-lymphocytes in vitro. Experiments using lymphocyte cell cultures reveal that the C strain of herpesvirus is also capable of transforming human T-lympphocytes. Results show that infection of human lymphocytes and thymocytes with the group C strain yields immortalized T-cells that express either CD4 of CD8 phenotype. This finding proves that Herpesvirus saimiri may be used to transform human T-cells to produce immortalized lymphocyte cell lines that can be used in immunological and developmental studies.

Characterization of the human interleukin-4 gene (IL-4) has revealed a unique11-base pair cis-acting element that is responsible for gene responsiveness to T-cell activation signals. This segment, also termed the P sequence, is locatedin the 5' region upstream from the IL-4 gene and has been localized to be between positions -79 and -69 from the gene transcription start site. Studies show that a DNA binding protein, NF(P), recognizes the P sequence and induces gene transcription in response to T-cell signals.

The mechanism of T-cell activation by human T-cell leukemia virus type I (HTLV-I) was examined in freshly isolated blood T-cells and in naturally infected T-cell clones. The results showed that HTLV-I- infected T-cells could proliferate in the absence of T-cell growth factors. Such activated T-cells could also stimulate noninfected T cells by interactionsinvolving the CD2 pathway. Therefore, HTLV-I activated T cells may contribute to the progression of HTLV-I-associated myelopathy by inducing a sustained activated state of T cells that recognized central nervous system autoantigens.

The article highlights the importance and the functions of the transcription factor, T-cell factor-3 (Tcf3) in the core regulatory circuit of the embryonic stem (ES) cells. Tcf3 is shown to be extremely critical for the process, as it helps in maintaining a balance between pluripotency and differentiation in the pathway.

The analogues of (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate (HMBPP) are synthesized, where the diphosphate group is replaced by isosteric moieties. The potential of the analogues to stimulate V[gamma]9/V[delta]2 T cell response or to inhibit GcpE and LytB, the last enzymes in the non-mevalonate pathway, is evaluated.

Protein phosphatase and myosin phophatase targeting subunit 1, two components of the myosin phosphatase complex, are identified as histone deacetylase 7 (HDAC7)-associated proteins in thymocytes. The dephosphorylation of HDAC7 by myosin phosphatase, its nucleocytoplasmic shuttling and its role as a transcriptional repressor that inhibits apoptosis in thymocytes are explained.

Signaling through the cell surface protein CD28 is important in the initial stages of T cell activation. However, other pathways of costimulation appear to be required for maintaining the activated [...]

T cell-mediated suppression has been of interest for some time, yet direct demonstration of specific mechanisms has been clouded in part by the diversity of experimental systems. Although suppression is [...]