CD45RC

Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion...

Gold or mercury salts trigger a dramatic IgE response and a CD4 T-cell-dependent nephropathy in Brown-Norway (BN), but not in Lewis (LEW) rats. We previously identified the 1.1-Mb Iresp3 (immunoglobin response QTL3) locus on chromosome 9 that controls these gold salt-triggered immune disorders. In the present work, we investigated the genetic control of HgCl(2)-induced immunological disorders and assessed the relative contribution of the CD45RC(high) and CD45RC(low) CD4 T-cell subpopulations in this control...

Detailed information concerning the development of the immune system in young pigs is still rudimental. In the present study, we analyzed changes in phenotype and absolute numbers of natural killer cells, γδ T cells, T helper cells, regulatory T cells and cytolytic T cells in the blood of pigs from birth to six months of age. For each lymphocyte subpopulation, a combination of lineage and differentiation markers was investigated by six-color flow cytometry. Major findings were: (i) absolute numbers of γδ T cells strongly increased from birth until 19-25 weeks of age, indicating an important role for these cells during adolescence; (ii) phenotype of T helper cells changed over time from CD8α(-)SLA-DR(-)CD27(+) towards CD8α(+)SLA-DR(+)CD27(-) but CD45RC(-) T helper cells were found immediately after birth, therefore questioning the role of this marker for the identification of T-helper memory cells; (iii) for cytolytic T cells, putative phenotypes for early effector (CD3(+)CD8αβ(+)perforin(+)CD27(dim)) and late effector or memory cells (CD3(+)CD8αβ(+)perforin(+)CD27(-)) could be identified...

Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus...

Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine...

Recent studies in the field of CD8(+) Tregs have allowed a better identification and characterization of this subset of regulatory cells. Their key role in the regulation of allogeneic responses is now well established. To take full advantage of CD8(+) Treg cells in future therapeutic applications, a better knowledge is required, particularly concerning the contribution of the T-cell receptor (TCR) in cell function as well as the role and importance of its antigenic specificity. Here, we focused on the CD8(+)CD45RC(low) Tregs, which in rats induce an indefinite long-term allograft acceptance...

The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (T(EM)) without affecting the function of naïve T cells (T(N)) and central memory T cells (T(CM)). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the T(EM) phenotype (CD45RC(-)CD62L(-))...

Enterotoxigenic Escherichia coli (ETEC) infection is the most common type of porcine postweaning colibacillosis (PWC). Among fimbriae of porcine ETEC strains the best studied family of fimbriae are the members of F4 adhesins, existing in at least three variants: ab, ac, ad. Active immunization against porcine PWC is difficult due to: i) ETEC strains are only one of the essential predisposing factors, ii) the success of vaccinal antigen uptake depends on the presence of enterocyte receptors for F4 adhesins, iii) the intestinal immune system may react with tolerance or hypersensitivity to the same antigens depending on the dose and form of the vaccinal immunogen, and iv) kinetics of the specific immune responses may be different in the case of F4 (earlier) and the other ETEC adhesins, particularly F18 (later)...

Colidiarrhea and colienterotoxemia caused by F4+ and/or F18+ enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac+ non- ETEC vaccine candidate strain against challenge infection with F4ac+ ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine...

BACKGROUND: Donor-specific blood transfusion (DST) prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported...

In animal models of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC), AAV patients and in Systemic lupus erythematous (SLE) patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals...

Vaccenic acid (VA) is a ruminant-derived trans-fat and precursor of conjugated linoleic acid (CLA). The objective of the present study was to explore the effects of VA on immune function in a model of the metabolic syndrome, JCR:LA-cp rats. Lean (2:1 mix of +/cp and +/+) and obese (cp/cp) rats, aged 8 weeks, were fed a control (0% VA) or a VA diet (1.5% (w/w) VA) for 3 weeks (twenty rats per group). Splenocytes and mesenteric lymph node (MLN) immune cell phenotypes (flow cytometry), ex vivo cytokine production (ELISA) and phospholipid fatty acid concentrations were measured...

Serglycin (SG) is a proteoglycan that is located predominantly in the secretory granules of hematopoietic cells. Previous studies have established a crucial role for SG in promoting the storage of various secretory granule compounds that are of importance in the immune defense system. Here, we show that mice lacking SG spontaneously develop enlargement of multiple lymphoid organs, including the spleen, Peyer's patches (PP), and bronchus-associated lymphoid tissue. In the spleen, the lack of SG resulted in a significant decrease in the proportion of CD4(+) cells as well as an increase of the CD45RC(+) leukocyte population, indicating an expansion of naïve lymphocytes...

Natural killer (NK) cells represent an important cell population of the innate immune system with the ability to attack spontaneously pathogen-infected and malignant body cells as well as to produce immune-regulatory cytokines. T lymphocytes belong to the adaptive immune system and perform a wide array of functions in immune regulation, inflammation and protective immune responses. In this review we summarize the current knowledge about the phenotype and functional characteristics of these two cell populations in swine...

Zn-deficient (ZD) rats have a lower proportion of splenic CD90+T-cells which could be due to fewer new T-cells exiting the thymus, defective post-thymic maturation or increased cell death. Post-thymic maturation of splenic lymphocytes and their viability were determined by flow cytometry in weanling rats assigned to ZD ( < 1 mg Zn/kg; ad libitum), diet-restricted (DR; 30 mg Zn/kg; limited to the amount of feed as consumed by ZD rats), marginally Zn-deficient (MZD; 10 mg Zn/kg; ad libitum) or control (30 mg Zn/kg; ad libitum) groups for 3 weeks...

We explored the parameters of central and peripheral tolerance in patients with stable relapsing-remitting multiple sclerosis, treated or not with IFN-beta. TREC-positive T cells were lower in patients compared with controls, mainly in CD4+ subset, compatible with a thymus dysfunction or an expansion of peripheral lymphocytes. Compared to controls, the frequency of activated CD4+CD25+ T cells was higher in patients without modification of the CD4+CD25(high) T cell proportion. The IFN-beta-treatment did not modify the TREC-positive cell frequency nor the naive/memory T cell subset percentage but was associated with lower blood lymphocyte count and a lower frequency of CD4+CD45RC(high) subset...

Over the last years regulatory T cells (Tregs) were defined as CD4(+)CD25(+) T lymphocytes expressing the transcription factor Foxp3 (Forkhead Box P3) with the ability to downregulate various immune responses. In swine the existence of CD4(+)CD25(+) T lymphocytes was described before but nothing is known about the function of this minor cell population to date. Therefore, we studied porcine CD4(+)CD25(+) T cells with regard to major attributes of murine and human Tregs: their phenotype concerning the expression of several T-cell specific antigens, including Foxp3, their IL-10 production and their suppressive capacity...

T cells have a central role in the pathogenesis of autoimmune arthritis, and several abnormalities in T cell homeostasis have been described in rheumatoid arthritis (RA). We hypothesized that T cell phenotypes, including frequencies of different subsets of T regulatory (Treg) cells and in vitro functional responses could be genetically determined. Furthermore, we considered that the genetic contribution would be accounted for by one of the arthritis regulatory quantitative trait loci (QTL), thus providing novel clues to gene mode of action...

The aetiology of porcine post-weaning multisystemic wasting syndrome (PMWS) is poorly understood. Porcine circovirus type 2 (PCV-2) is an essential component of the experimental disease model for PMWS: however, evidence from experimental and field studies indicates that additional factors play a critical role in the aetiopathogenesis of PMWS. Current candidates include (1) immune stimulation (for example, via co-infection or vaccination), and (2) a novel infectious agent. A prospective, longitudinal case-control study was designed to investigate molecular triggers in leucocytes of neonatal piglets that may predispose to the development of PMWS...

Treatment with CD40Ig results in indefinite allograft survival in a complete MHC-mismatched heart allograft model in the rat. Here we show that serial second, third, and fourth adoptive transfers of total splenocytes from CD40Ig-treated recipients into secondary recipients led to indefinite donor-specific allograft acceptance. Purification of splenocyte subpopulations from CD40Ig-treated recipients demonstrated that only the adoptively transferred CD8(+)CD45RC(low) subset resulted in donor-specific long-term survival, whereas CD8(+)CD45RC(low) T cells from naive animals did not...