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Memory Phenotype (memory + phenotype)
Selected AbstractsExpression of CD8, identifies a distinct subset of effector memory CD4+ T lymphocytesIMMUNOLOGY, Issue 2 2006Iole Macchia Summary Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8,, homodimer, while the minor population was CD4lo CD8hi and expressed the CD8,, heterodimer. The majority of CD4hi CD8,lo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7, CD28, HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8,lo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8,lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8,lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8, represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection. [source] Human B cells express a CD45 isoform that is similar to murine B220 and is downregulated with acquisition of the memory B-cell marker CD27,CYTOMETRY, Issue 1 2003Jack J. H. Bleesing Abstract Background Differences between human and murine B cells exist at all stages of B-cell development, including the stage of memory B-cell formation. B cells in mice are identified with the pan,B-cell,specific CD45 isoform, B220. In initial studies in humans, it appeared that B220 expression did not include all B cells. This study was performed to expand on those preliminary findings. Methods Multiparameter flow cytometric detection of B220 expression on B cells was combined with a variety of B-cell markers. Results In contrast to mice, B220 was not a pan,B-cell marker in humans but was downregulated in the majority of B cells that acquired the human memory B-cell marker, CD27, whereas a minor memory B-cell subset remained B220+, suggesting differences in differentiation. Conclusions The B220 isoform in humans is developmentally regulated in humans, tied to the acquisition of a memory phenotype, and as such can be used as a differentiation-specific CD45 isoform, akin to the use of CD45 isoforms to distinguish between naive and memory T-cell subsets. Patients with immunodeficiency disorders, associated with defective memory B-cell generation and absent or reduced CD27+ B cells, showed a corresponding lack of B220 downregulation consistent with altered differentiation of B-cell subsets. Cytometry Part B (Clin. Cytometry) 51B:1,8, 2003. Published 2002 Wiley-Liss, Inc. [source] IL-15 is critical for the maintenance and innate functions of self-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Momoe Itsumi Abstract IL-15 is a pleiotropic cytokine involved in host defense as well as autoimmunity. IL-15-deficient mice show a decrease of memory phenotype (MP) CD8+ T cells, which develop naturally in naïve mice and whose origin is unclear. It has been shown that self-specific CD8+ T cells developed in male H-Y antigen-specific TCR transgenic mice share many similarities with naturally occurring MP CD8+ T cells in normal mice. In this study, we found that H-Y antigen-specific CD8+ T cells in male but not female mice decreased when they were crossed with IL-15-deficient mice, mainly due to impaired peripheral maintenance. The self-specific TCR transgenic CD8+ T cells developed in IL-15-deficient mice showed altered surface phenotypes and reduced effector functions ex vivo. Bystander activation of the self-specific CD8+ T cells was induced in vivo during infection with Listeria monocytogenes, in which proliferation but not IFN-, production was IL-15-dependent. These results indicated important roles for IL-15 in the maintenance and functions of self-specific CD8+ T cells, which may be included in the naturally occurring MP CD8+ T-cell population in naïve normal mice and participate in innate host defense responses. [source] Intestinal double-positive CD4+CD8+ T,cells are highly activated memory cells with an increased capacity to produce cytokinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Bapi Pahar Dr. Abstract Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T,cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T,cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T,cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T,cells. Intestinal DP T,cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T,cells populations compared to CD4+ single-positive T,cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T,cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T,cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. [source] CD4 T,cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T,cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003Kajsa Wing Abstract Regulatory T,cells expressing CD25 have been shown to protect rodents from organ-specific autoimmune diseases. Similar CD25+ cells with a memory phenotype exerting suppressive function after polyclonal or allogeneic stimulation are also present in adult human blood. We demonstrate that adult human CD25+ cells regulate the response to myelin oligodendrocyte glycoprotein (MOG), as depletion of CD25+ cells increases responses of PBMC and the addition of purified CD25+ cells suppresses MOG-specific proliferation and IFN-, production of CD4+CD25, T,cells. In contrast, cord blood CD25+ cells do not inhibit responses to self antigens, and only a small subpopulation of cord CD25+ cells expresses the typical phenotype of adult regulatory T,cells (CD45RA, and GITR+) enabling suppression of polyclonal responses. We conclude that activation of self-reactive T,cells in normal healthy individuals is prevented by the presence of self-antigen-specific CD25+ regulatory T,cells and that the majority of these cells mature after birth. [source] Optimization of in vitro expansion of macaque CD4+ T cells using anti-CD3 and co-stimulation for autotransfusion therapyJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2006Nattawat Onlamoon Abstract Background, Our laboratory has previously shown that adoptive transfer of in vitro -expanded autologous purified polyclonal CD4+ T cells using anti-CD3/CD28-coated beads induced antiviral responses capable of controlling SIV replication in vivo. Methods, As CD4+ T cells comprise several phenotypic and functional lineages, studies were carried out to optimize the in vitro culture conditions for maximal CD4+ T-cell expansion, survival and delineate the phenotype of these expanded CD4+ T cells to be linked to maximal clinical benefit. Results and Conclusions, The results showed that whereas anti-monkey CD3,/, was able to induce T-cell proliferation and expansion in combination with antibodies against multiple co-stimulatory molecules, monkey CD3, cross reacting antibodies failed to induce proliferation of macaque CD4+ T cells. Among co-stimulatory signals, anti-CD28 stimulation was consistently superior to anti-4-1BB, CD27 or ICOS while the use of anti-CD154 failed to deliver a detectable proliferation signal. Increasing the relative anti-CD28 co-stimulatory signal relative to anti-CD3 provided a modest enhancement of expansion. Additional strategies for optimization included attempts to neutralize free radicals, enhancement of glucose uptake by T cells or addition of T-cell stimulatory cytokines. However, none of these strategies provided any detectable proliferative advantage. Addition of 10 autologous irradiated feeder cells/expanding T cell provided some enhancement of expansion; however, given the high numbers of T cell needed, this approach was deemed impractical and costly, and lower ratios of feeder to expanding T cells failed to provide such benefit. The most critical parameter for efficient expansion of purified CD4+ T cells from multiple monkeys was the optimization of space and culture conditions at culture inception. Finally, anti-CD3/28-expanded CD4+ T cells uniformly exhibited a central memory phenotype, absence of CCR5 expression, marked CXCR4 expression in vitro, low levels of caspase 3 but also of Bcl-2 expression. [source] Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphomaJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2002B. Ling Abstract: Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post-infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV-1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS. [source] Memory T-Cell Predominance Following T-Cell Depletional Therapy Derives from Homeostatic Expansion of Naive T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A. Sener T-cell depletion reportedly leads to alterations in the T-cell compartment with predominant survival of memory phenotype CD4 T cells. Here, we asked whether the prevalence of memory T cells postdepletion results from their inherent resistance to depletion and/or to the homeostatic expansion of naive T cells and their phenotypic conversion to memory, which is known to occur in lymphopenic conditions. Using a ,mosaic memory' mouse model with trackable populations of alloreactive memory T cells, we found that treatment with murine antithymocyte globulin (mATG) or antilymphocyte serum (ALS) effectively depleted alloreactive memory CD4 T cells, followed by rapid homeostatic proliferation of endogenous CD4 T cells peaking at 4 days postdepletion, with no homeostatic advantage to the antigen-specific memory population. Interestingly, naive (CD44lo) CD4 T cells exhibited the greatest increase in homeostatic proliferation following mATG treatment, divided more extensively compared to memory (CD44hi) CD4 T cells and converted to a memory phenotype. Our results provide novel evidence that memory CD4 T cells are susceptible to lymphodepletion and that the postdepletional T-cell compartment is repopulated to a significant extent by homeostatically expanded naive T cells in a mouse model, with important important implications for immune alterations triggered by induction therapy. [source] Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remissionARTHRITIS & RHEUMATISM, Issue 6 2007Wayel H. Abdulahad Objective Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25high and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed. Methods Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25high,CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls. Results In WG patients, a significant increase was observed in the percentage of circulating CD25high,CD4+ and CD25low,CD4+ T cells, whereas CD25,,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25high,FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25high,CD4+ T cells was tested, CD25high,CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells. Conclusion These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis. [source] | ||||||||||