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Macrophages characterized as M2 and M2-like regulate immune responses associated with immune suppression and healing; however, the relationship of this macrophage subset to [CD169.sup.+] tissue-resident macrophages and their contribution to shaping alloimmune responses is unknown. Here we identified a population of M2-like tissue-resident macrophages that express high levels of the phosphatidylserine receptor TIM-4 and CD169 ([TIM-4.sup.hi[CD169.sup.+]).] Labeling and tracking of [TIM-4.sup.hi][CD169.sup.+] macrophages in mice revealed that this population is a major subset of tissue-resident macrophages, homes to draining LNs following oxidative stress, exhibits an immunoregulatory and hypostimulatory phenotype that is maintained after migration to secondary lymphoid organs, favors preferential induction of antigen-stimulated Tregs, and is highly susceptible to apoptosis. Moreover, [CD169.sup.+] tissue-resident macrophages were resistant to oxidative stress-induced apoptosis in mice lacking TIM-4. Compared with heart allografts from WT mice, [Tim4.sup.-/-] heart allografts survived much longer and were more easily tolerized by non-immunosuppressed recipients. Furthermore, [Tim4.sup.-/-] allograft survival was associated with the infiltration of Tregs into the graft. Together, our data provide evidence that M2-like [TIM-4.sup.hi][CD169.sup.+] tissue-resident macrophages are immunoregulatory and promote engraftment of cardiac allografts, but their influence is diminished by TIM-4-dependent programmed cell death., Introduction Recent advances in macrophage biology have revealed several subpopulations. One prominent categorization separates [Ly6C.sup.+] monocyte-derived macrophages into M1 (destructive, inflammatory) and M2 (healing, immunoregulatory) subsets. Monocytes differentiate into an [...]

Tregs play a pivotal role in inducing and maintaining donorspecific transplant tolerance. The T cell immunoglobulin and mucin domain-3 protein (TIM-3) is expressed on many fully activated effector T cells. Along with program death 1 (PD-1), TIM-3 is used as a marker for exhausted effector T cells, and interaction with its ligand, galectin-9, leads to selective death of TIM-3+ cells. We report herein the presence of a galectin-9-sensitive CD4+FoxP3+TIM-3+ population of T cells, which arose from CD4+FoxP3 +TIM-3- proliferating T cells in vitro and in vivo and were often PD-1+. These cells became very prominent among graft-infiltrating Tregs during allograft response. The frequency and number of TIM-3+ Tregs peaked at the time of graft rejection and declined thereafter. Moreover, these cells also arise in a tolerance-promoting donorspecific transfusion model, representing a pool of proliferating, donorspecific Tregs. Compared with TIM-3- Tregs, TIM-3+ Tregs, which are often PD-1+ as well, exhibited higher in vitro effector function and more robust expression of CD25, CD39, CD73, CTLA-4, IL-10, and TGF-β but not galectin-9. However, these TIM-3+ Tregs did not flourish when passively transferred to newly transplanted hosts. These data suggest that a heretofore unrecognized graftinfiltrating, short-lived subset of Tregs can restrain rejection., Introduction A hallmark of an adaptive immune response is differentiation and clonal expansion of T effector cell (Teff) populations, including Th1, Th2, Th17 cells, and Tregs (1-4). T cell immunoglobulin [...]

Stem cells reside in a specialized regulatory microenvironment or niche (1,2), where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity (1-3). The niche may also protect stem cells from environmental insults (3) including cytotoxic chemotherapy and perhaps pathogenic immunity (4). The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression (4). We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche (1,2,5-7) in the bone marrow, a site where immune reactivity exists (8,9). We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T ([T.sub.reg]) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with [T.sub.reg] cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. [T.sub.reg] cells seem to participate in creating a localized zone where HSPCs reside and where [T.sub.reg] cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack., Despite rapid advances in our understanding of adult stem-cell biology, the immunological attributes of somatic stem-cell niches have remained largely unexplored. We hypothesized that the HSPC niche within the bone [...]

Here we present methods to longitudinally track islet allograft-infiltrating T cells in live mice by endoscopic confocal microscopy and to analyze circulating T cells by in vivo flow cytometry. We developed a new reporter mouse whose T cell subsets express distinct, 'color-coded' proteins enabling in vivo detection and identification of effector T cells ([T.sub.eff] cells) and discrimination between natural and induced regulatory T cells ([nT.sub.reg] and [iT.sub.reg] cells). Using these tools, we observed marked differences in the T cell response in recipients receiving tolerance-inducing therapy (CD154-specific monoclonal antibody plus rapamycin) compared to untreated controls. These results establish real-time cell tracking as a powerful means to probe the dynamic cellular interplay mediating immunologic rejection or transplant tolerance., ********** Understanding the cellular immune response to transplanted tissue has a key role in developing strategies to improve transplant outcomes. Tissue biopsy is the standard method for accessing immune cell [...]

While many candidate type 1 diabetes (T1D) susceptibility genes have been identified, evidence suggests that environmental stimuli, such as viral infections, may also be involved in T1D pathogenesis. However, how viral infections may prevent or trigger the diabetogenic process remains unclear. In this issue of the JCI, Filippi et al. show that infection of NOD mice with Coxsackie virus B3 or lymphocytic choriomeningitis virus, neither of which directly destroys insulin-secreting pancreatic [beta] cells, triggers the activation of two distinct immunoregulatory mechanisms, involving both the innate and adaptive immune system, that protect against the development of T1D in these animals (see the related article beginning on page 1515)., Immune-mediated destruction of insulin-secreting pancreatic [beta] cells results in type 1 diabetes (T1D). Genetic factors, including genes that regulate facets of the immune response, influence the susceptibility of an individual [...]

Invasive insulitis is a destructive T cell-dependent autoimmune process directed against insulin-producing [beta] cells that is central to the pathogenesis of type 1 diabetes mellitus (T1DM) in humans and the clinically relevant nonobese diabetic (NOD) mouse model. Few therapies have succeeded in restoring long-term, drug-free euglycemia and immune tolerance to [beta] cells in overtly diabetic NOD mice, and none have demonstrably enabled enlargement of the functional [beta] cell mass. Recent studies have emphasized the impact of inflammatory cytokines on the commitment of antigen-activated T cells to various effector or regulatory T cell phenotypes and insulin resistance and defective insulin signaling. Hence, we tested the hypothesis that inflammatory mechanisms trigger insulitis, insulin resistance, faulty insulin signaling, and the loss of immune tolerance to islets. We demonstrate that treatment with [alpha]1-antitrypsin (AAT), an agent that dampens inflammation, does not directly inhibit T cell activation, ablates invasive insulitis, and restores euglycemia, immune tolerance to [beta] cells, normal insulin signaling, and insulin responsiveness in NOD mice with recent-onset T1DM through favorable changes in the inflammation milieu. Indeed, the functional mass of [beta] cells expands in AAT-treated diabetic NOD mice. autoimmunity | type 1 diabetes | inflammation

T cell Ig mucin (Tim) molecules modulate [CD4.sup.+] T cell responses. In keeping with the view that Tim-1 generates a stimulatory signal for [CD4.sup.+] T cell activation, we hypothesized that an agonist Tim-1-specific mAb would intensify the [CD4.sup.+] T cell--dependant allograft response. Unexpectedly, we determined that a particular Tim-1-specific mAb exerted reciprocal effects upon the commitment of alloactivated T cells to regulatory and effector phenotypes. Commitment to the Th1 and Th17 phenotypes was fostered, whereas commitment to the Treg phenotype was hindered. Moreover, ligation of Tim-1 in vitro effectively deprogrammed Tregs and thus produced Tregs unable to control T cell responses. Overall, the effects of the agonist Tim-1-specific mAb on the allograft response stemmed from enhanced expansion and survival of T effector cells; a capacity to deprogram natural Tregs; and inhibition of the conversion of naive [CD4.sup.+] T cells into Tregs. The reciprocal effects of agonist Tim-1-specific mAbs upon effector T cells and Tregs serve to prevent allogeneic transplant tolerance., Introduction T cell Ig mucin (Tim) molecules are structurally related to type I membrane glycoproteins expressed on T cells (1). Polymorphisms within the Tim gene locus are associated with susceptibility [...]

A field study was conducted to examine the turbulent properties of the flow around a naturally formed cluster bedform. This was carried out on a mountain river using a 3D acoustic Doppler velocimeter (ADV). Concurrent with this objective, the ability of the ADV to make measurements in a shallow flow over a cobble bed ([h.sub.o]/[d.sub.84] = 1.75) was examined. ADV measurements in natural clear-water shallow flows around obstacles are inherently difficult to obtain due to (1) signal interference between the acoustic reflections from the boundary and the ADV sample volume; (2) regions of high turbulent intensity, such as in local detached shear layers; and (3) low concentrations of suspended particles passing through the ADV sampling volume. These processes result in velocity time series that contain a significant amount of spikes, lower-than-average signal-to-noise ratios, and lower than average correlation values. A filtering process that optimized the removal of bad points while retaining a sufficient number of points to describe the velocity time series histogram was developed. In general, flow over the study section can be described by an inner roughness layer dominated by large roughness and detached flow, and an outer flow that exhibits a form of log scaling. It was found that the cluster acts to locally modify this structure by shifting the elevation of the roughness layer and the zone of primary production and dissipation of turbulent energy up towards the center of the water column. Mean and turbulent statistics, energy distributions, spectral properties, and a quadrant analysis are presented to characterize the flow around the cluster. CE Database subject headings: Turbulent flow; River beds; Bedforms; Gravel; Mountain streams; Measuring instruments; Flow measurement.

In nonobese diabetic (NOD) mice with overt new-onset type 1 diabetes mellitus (T1DM), short-term treatment with a 'tripletherapy' regimen [rapamycin plus agonist IL-2-related and antagonist-type, mutant IL-15-related Ig fusion proteins (IL-2.Ig and mutIL-15.Ig)] halts autoimmune destruction of insulin-producing beta cells and restores both euglycemia and immune tolerance to beta cells. Increases in the mass of insulin-producing beta cells or circulating insulin levels were not linked to the restoration of euglycemia. Instead, the restoration of euglycemia was linked to relief from an inflammatory state that impaired the host's response to insulin. Both restoration of immune tolerance to beta cells and relief from the adverse metabolic effects of an inflammatory state in insulin-sensitive tissues appear essential for permanent restoration of normoglycemia in this TIDM model. Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in TIDM. autoimmunity | diabetes | NOD mice | tolerance | transplantation

Treatment with ex vivo-generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)[sub.35-55]/IA[sup.b] (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer-reactive, Foxp3[sup.+] T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3[sup.+] T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4[sup.+]Foxp3[sup.+] T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation., Author(s): Thomas Korn [1]; Jayagopala Reddy [1]; Wenda Gao [2]; Estelle Bettelli [1]; Amit Awasthi [1]; Troels R Petersen [3]; B Thomas Backstrom [3]; Raymond A Sobel [4]; Kai W [...]

The present study examines the flow around a self-occurring cluster bed form and the use of general computation fluid dynamics methods for hydraulic and geophysical flow applications. This is accomplished through a comprehensive experimental/numerical investigation. In the laboratory, cluster bed forms are first formed from movable sediment, and laser Doppler velocimeter measurements of two-dimensional fluid velocity are then taken around a formed cluster. A three-dimensional (3D) Reynolds averaged Navier-Stokes simulation of the physical cluster and flow conditions is then conducted using near-wall, shear stress transport (SST) turbulence modeling with the inclusion of hydraulic roughness, [k.sub.s] (R = 31,150, [k.sub.s]/h = 0.1, [k.sup.+.sub.s] = 274, i.e., in the fully rough regime). SST near-wall modeling is advantageous compared to the more widely used wall functions approach for flows with significant roughness and flow separation because the model equations can be integrated down to the wall. Therefore, SST near-wall modeling makes no a priori assumption that the law of the wall is valid throughout the wall region of the flow. Additionally, it has the ability to intrinsically handle boundary roughness through the boundary condition for turbulent specific dissipation at the wall, allowing for wall functions to be bypassed in accounting for roughness effects. The study shows that in the wall region surrounding the cluster, flow is 3D and quite complex, with different scales of embedded flow structures dominating the cluster wake and leading to flow heterogeneities in pressure and bed-shear stress. Results also indicate that near-wall modeling with SST compared favorably with the experimental flow data without tuning of model constants. DOI: 10.1061/(ASCE)0733-9429(2007) CE Database subject headings: Bedforms; Microstructures; Turbulent flow; Numerical models; Simulation; Computational fluid dynamics technique; Hydraulic engineering.

Peripheral tolerance can be achieved in many but not all murine allograft models. The requirements for controlling more aggressive immune responsiveness and generating peripheral tolerance in stringent allograft models are unknown. Understanding these requirements will provide insight toward ultimately achieving tolerance in humans, which are also resistant. We now demonstrate that the combination of donor-specific transfusion, anti-CD45RB, and anti-CD154 uniformly achieves >90-d survival of BALB/c skin allografts on C57BL/6 recipients. Recipients exhibit marked hyporesponsiveness to alloantigen in vitro. In distinct contrast to less rigorous models, engraftment remains absolutely dependent on cytotoxic T lymphocyte antigen 4 signaling, even after grafts are healed, suggesting that prolonged engraftment cannot simply be attributed to more effective depletion of alloreactive T cells but is actively maintained by regulation. Concordantly, we show that both CD4 and CD8 regulatory cells are required and can transfer donor-specific tolerance to naive recipients. Nonetheless, most recipients ultimately develop gradual graft loss (median survival time = 140 d), suggesting that alloreactive cells emerging from the thymus eventually overwhelm regulatory capacity. In agreement, adding thymectomy to the regimen results in permanent engraftment (>250 d) and donor-specific tolerance not observed previously in this model. These results highlight the potency of both CD4 and CD8 regulatory cells but also suggest that in stringent settings, regulatory T cell longevity and capacity for infectious tolerance compete with prolonged graft immunogenicity and thymic output. These results provide insight into the mechanisms of tolerance in stringent models and provide a rational basis for innovative tolerogenic strategies in humans. transplantation | rodent | CD4 cell | CD8 cell | regulatory T cell

Interleukin (IL)-2 and IL-15 are redundant in stimulating T-cell proliferation in vitro. Their precise role in vivo in governing T-cell expansion and T-cell homeostasis is less clear. Each may have distinct functions and regulate distinct aspects of T-cell activation. The functional receptors for IL-2 and IL-15 consist of a private [alpha]-chain, which defines the binding specificity for IL-2 or IL-15, and shared IL-2 receptor [beta]- and [gamma]-chains. The [gamma]-chain is also a critical signaling component of IL-4, IL-7 and IL-9 receptors. Thus, the [gamma]-chain is called the common [gamma] or [gamma]-c. As these receptor subunits can be expressed individually or in various combinations resulting in the formation of receptors with different affinities, distinct signaling capabilities or both, we hypothesized that differential expression of IL-2 and IL-15 receptor subunits on cycling T cells in vivo may direct activated T cells to respond to IL-2 or IL-15, thereby regulating the homeostasis of T-cell response in vivo. By observing in vivo T-cell divisions and expression of IL-2 and IL-15 receptor subunits, we demonstrate that IL-15 is a critical growth factor in initiating T cell divisions in vivo, whereas IL-2 limits continued T-cell expansion via downregulation of the [gamma]-c expression. Decreased [gamma]-c expression on cycling T cells reduced sustained Bcl-2 expression and rendered cells susceptible to apoptotic cell death. Our study provides data that IL-2 and IL-15 regulate distinct aspects of primary T-cell expansion in vivo., Author(s): Xian Chang Li (corresponding author) [1]; Gulcin Demirci [1]; Sylvie Ferrari-Lacraz [1]; Chris Groves [2]; Anthony Coyle [2]; Thomas R. Malek [3]; Terry B. Strom [1] In contrast to [...]

Immune tolerance cannot be induced in mice with defective T-cell apoptosis. This shows that deletion of alloreactive T cells is necessary for inducing tolerance to a transplant.

Co-stimulation blockade of the CD28-B7 and CD40-CD40 ligand interactions prevents the proliferation of alloreactive T cells. Adding rapamycin causes apoptosis of alloreactive T cells and allograft tolerance.

During transplant rejection, migrating T cells infiltrate the grafted organ, but the signals that direct this migration are incompletely understood. In this issue of the JCI, Walch et al. debunk [...]

Procedures to diagnose renal allograft rejection depend upon detection of graft dysfunction and the presence of a mononuclear leukocytic infiltrate; however, the presence of a modest cellular infiltrate is often not conclusive and can be detected in non-rejecting grafts. We have pursued a molecular approach utilizing reverse transcription (RT)-PCR to test the diagnostic accuracy of multiple immune activation gene analysis as means to diagnose renal allograft rejection. The magnitude of intragraft gene expression of 15 immune activation genes was quantified by competitive RT-PCR in 60 renal allograft core biopsies obtained for surveillance or to diagnose the etiology of graft dysfunction. Results were compared with a clinicopathological analysis based upon the histological diagnosis (Banff criteria) and the response to antirejection treatment. During acute renal allograft rejection intragraft expression of the interleukin (IL)-7 (P < 0.001), IL-10 (P < 0.0001), IL-15 (P < 0.0001), Fas ligand (P < 0.0001), perforin (P < 0.0001), and granzyme B (P < 0.0015), but not IL-2, interferon [Gamma], or IL-4, genes is significantly heightened. Amplified RANTES and IL-8 gene transcripts are sensitive but nonspecific markers of rejection. A simultaneous RT-PCR evaluation of perforin, granzyme B, and Fas ligand identifies acute rejection, including cases with mild infiltration, with extraordinary sensitivity (100%) and specificity (100%). Effective antirejection therapy results in a rapid down-regulation of gene expression. The combined analysis of Fas ligand, perforin, and granzyme B gene expression by quantitative RT-PCR provides a reliable tool for diagnosis and follow-up of acute renal allograft rejection. Its accuracy and a potential rapid application within few hours suggest its use in the clinical management of renal transplant patients.

Studies focusing on the immunological processes of kidney transplantation highlight the improvements that have been made in outcome for transplants. The process by which a kidney transplant is rejected is analyzed, and pharmacological agents that can combat the rejection are discussed. Examples of these are cyclosporine, tacrolimus, corticosteroids, azathioprine, and several newer drugs. The rate of successful outcomes after kidney transplants has increased in recent years, especially among transplants from cadavers and second and third transplant attempts. End-stage renal disease creates a need for renal transplantation. HLA (human leukocyte antigen) matching and cross-matches between donors and recipients affect the transplant prognosis. Conditions which may complicate renal transplantation are infection, pregnancy, chronic rejection, high blood pressure, blood lipid disorders, recurrence of disease, liver disease, cancer and reduced bone mass. Better immunosuppressive regimens may be expected in the near future.

A study was done on the beta chain variable region 11-positive islet-infiltrating T cell clone to better understand the mechanism behind their role in the induction and maintenance of tolerance. It was shown that T cells secrete an inhibitory factor that prevents interleukin (IL) 2/IL-4 driven proliferation of IL-2/IL-4 indicator T cell lines. These results suggest that some T cells exert suppressor activity towards interleukin factors and therefore towards immune tolerance.

HIV-1 IS A LYMPHOTROPHIC RETROVIRUS that initially may cause T cell activation [1, 2] but ultimately leads to a fatal collapse of the immune system. Interaction of HIV-1 with its [...]

Author(s): Thomas Korn [1, 4]; Estelle Bettelli [1, 4]; Wenda Gao [2, 4]; Amit Awasthi [3]; Anneli Jäger [1]; Terry B. Strom [2]; Mohamed Oukka (corresponding author) [3]; Vijay K. [...]

Author(s): Li-Fan Lu [1]; Evan F. Lind [1]; David C. Gondek [1]; Kathy A. Bennett [1]; Michael W. Gleeson [1]; Karina Pino-Lagos [1]; Zachary A. Scott [1]; Anthony J. Coyle [...]

Author(s): Estelle Bettelli [1, 4]; Yijun Carrier [1, 4]; Wenda Gao [2, 4]; Thomas Korn [1]; Terry B. Strom [2]; Mohamed Oukka (corresponding author) [3]; Howard L. Weiner [1]; Vijay [...]

With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus--1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of [CD4.sup.+] T cells, no virus-specific [CD4.sup.+] T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable [CD4.sup.+] T cell counts, preserved virus-specific [CD4.sup.+] T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge., Recent studies have demonstrated the critical role of virus-specific [CD8.sup.+] CTL responses in controlling HIV-1 replication in humans and simian immunodeficiency virus (SIV) replication in rhesus monkeys (1-5). It is [...]

The potential utility of plasmid DNA as an HIV-1 vaccination modality currently is an area of active investigation. However, recent studies have raised doubts as to whether plasmid DNA alone will elicit immune responses of sufficient magnitude to protect against pathogenic AIDS virus challenges. We therefore investigated whether DNA vaccine-elicited immune responses in rhesus monkeys could be augmented by using either an IL-2/Ig fusion protein or a plasmid expressing IL-2/Ig. Sixteen monkeys, divided into four experimental groups, were immunized with (i) sham plasmid, (ii) HIV-1 Env 89.6P and simian immunodeficiency virus mac239 Gag DNA vaccines alone, (iii) these DNA vaccines and IL-2/Ig protein, or (iv) these DNA vaccines and IL-2/Ig plasmid. The administration of both IL-2/Ig protein and IL-2/Ig plasmid induced a significant and sustained in vivo activation of peripheral T cells in the vaccinated monkeys. The monkeys that received IL-2/Ig plasmid generated 30-fold higher Env-specific antibody titers and 5-fold higher Gag-specific, tetramer-positive CD8+ T cell levels than the monkeys receiving the DNA vaccines alone. IL-2/Ig protein also augmented the vaccine-elicited immune responses, but less effectively than IL-2/Ig plasmid. Augmentation of the immune responses by IL-2/Ig was evident after the primary immunization and increased with subsequent boost immunizations. These results demonstrate that the administration of IL-2/Ig plasmid can substantially augment vaccine-elicited humoral and cellular immune responses in higher primates.

Research on immunotoxins may lead to the creation of drugs that can target cancer cells without damaging healthy cells. An immunotoxin is created by combining a human antibody to a tumor antigen with a toxic substance. The antibody binds to the tumor cells and the toxin destroys them.

Author(s): Xian Chang Li [1]; Terry B. Strom [1] THE SUCCESS of allogeneic hematopoietic stem cell engraftment across major histocompatibility complex barriers can be promoted by passenger cells that are [...]

Author(s): Yongsheng Li [1]; Terry B. Strom [1] Li and Strom reply Dharnidharka and colleagues raise an important point. Co-stimulation blockade using anti-CD154 and CTLA4-Ig, albeit remarkably effective in many [...]