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Memory CD8+ T Cells (memory + cd8+_t_cell)

Distribution by Scientific Domains

Medical Sciences	90%

Selected Abstracts

Differential Requirement of CD27 Costimulatory Signaling for Naïve Versus Alloantigen-Primed Effector/Memory CD8+ T Cells

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
K. Yamaura
CD8+ memory T cells endanger allograft survival by causing acute and chronic rejection and prevent tolerance induction. We explored the role of CD27:CD70 T-cell costimulatory pathway in alloreactive CD8+/CD4+ T-cell activation. CD27-deficient (CD27,/,) and wild-type (WT) B6 mice rejected BALB/c cardiac allografts at similar tempo, with or without depletion of CD4+ or CD8+ T cells, suggesting that CD27 is not essential during primary T-cell alloimmune responses. To dissect the role of CD27 in primed effector and memory alloreactive T cells, CD27,/, or WT mice were challenged with BALB/c hearts either 10 or 40 days after sensitization with donor-type skin grafts. Compared to WT controls, allograft survival was prolonged in day 40- but not day 10-sensitized CD27,/, recipients. Improved allograft survival was accompanied by diminished secondary responsiveness of memory CD8+ T cells, which resulted from deficiency in memory formation rather than their lack of secondary expansion. Chronic allograft vasculopathy and fibrosis were diminished in CD27,/, recipients of class I- but not class II-mismatched hearts as compared to WT controls. These data establish a novel role for CD27 as an important costimulatory molecule for alloreactive CD8+ memory T cells in acute and chronic allograft rejection. [source]

Type I Interferons Are Not Critical for Skin Allograft Rejection or the Generation of Donor-Specific CD8+ Memory T Cells

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
M. H. Oberbarnscheidt
Type I interferons (IFN-I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN-I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor-specific CD8+ T-cell responses in mice that lack the IFN-I receptor (IFN-IR,/,). We found that IFN-IR,/, mice reject fully allogeneic wild-type skin grafts at the same rate as wild-type recipients. Similarly, allograft rejection was not delayed if IFN-IR,/, male skin was transplanted to syngeneic IFN-IR,/, female mice. Quantitation of the male (H-Y)-specific CD8+ T-cell response in these mice revealed normal generation of donor-specific CD8+ effector T cells but fourfold reduction in CD8+ memory T cells. Memory CD8+ T cells generated in the absence of IFN-IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN-IR,/, mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN-1. Our findings indicate that IFN-I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor-specific CD8+ T cells into long-lived, functional memory T cells. [source]

CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004
Anna Ericsson
Abstract The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8+ intraepithelial lymphocytes (IEL), naïve murine CD8+ T cells and by a small population of effector/memory CD8+ T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8+ T cells following their activation in mesenteric lymph nodes and that effector CD8+ T cells upon initial entry into the small intestinal epithelium are CCR9+CD103,. CD103 was rapidly induced on wild-type CD8+ T cells subsequent to their entry into the small intestinal epithelium, however, CCR9,/, CD8+ T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8+ small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8+ IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa. [source]

FCRL6 distinguishes mature cytotoxic lymphocytes and is upregulated in patients with B-cell chronic lymphocytic leukemia

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008
Daniel M. Schreeder
Abstract Fc receptor-like 6 (FCRL6), the most recently characterized member of the FCRL family, is a cell surface glycoprotein with tyrosine-based regulatory potential. An extensive survey of human hematopoietic tissues disclosed that FCRL6 expression by NK- and T-cell subpopulations increases as a function of differentiation and is remarkably restricted to mature lymphocytes with cytotoxic capability. In particular, FCRL6 distinguishes perforin-expressing CD56dim NK cells, V,1+ and V,2+ ,, T cells, effector and effector memory CD8+ T cells, and rare cytotoxic CD4+ T cells in adult tissues. Analysis of this receptor in B-cell chronic lymphocytic leukemia (CLL) was also performed. FCRL6 was found to mark significantly expanded populations of cytotoxic CD8+ T, CD4+ T, and NK cells in patients with CLL. Despite sequence homology with the known Fc receptors for IgG and IgE, FCRL6 did not bind Ig. Although FCRL6 can be tyrosine-phosphorylated, its antibody-mediated ligation was unable to influence cellular activation. Collectively, these results demonstrate that FCRL6 is a distinct indicator of cytotoxic effector lymphocytes that is upregulated in diseases characterized by chronic immune stimulation. [source]

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008
Matthias
Abstract CD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27high whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27,/, memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory. [source]

Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2007
Martin
Abstract IL-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro T cell proliferation but is also essential for down-regulating T cell responses by inducing activation-induced cell death as well as regulatory T cells. The in vivo analysis of IL-2 function in regulating specific T cell responses has been hampered by the fact that mice deficient in IL-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. Here we generated chimeric mice harboring both IL-2R-competent and IL-2R-deficient T cells and assessed CD8+ T cell induction, function and maintenance after acute or persistent viral infections. Induction and maintenance of CD8+ T cells were relatively independent of IL-2R signaling during acute/resolved viral infection. In marked contrast, IL-2 was crucial for secondary expansion of memory CD8+ T cells and for the maintenance of virus-specific CD8+ T cells during persistent viral infections. Thus, depending on the chronicity of antigen exposure, IL-2R signaling is either essential or largely dispensable for induction and maintenance of virus-specific CD8+ T cell responses. [source]

Immune regulation by 4-1BB and 4-1BBL: complexities and challenges

IMMUNOLOGICAL REVIEWS, Issue 1 2009
Chao Wang
Summary:, The tumor necrosis factor receptor family member 4-1BB plays a key role in the survival of activated and memory CD8+ T cells. Depending on the disease model, 4-1BB can participate at different stages and influence different aspects of the immune response, likely due to the differential expression of receptor and ligand relative to other costimulatory molecules. Studies comparing mild versus severe influenza infection of mice suggest that the immune system uses inducible receptors such as 4-1BB to prolong the immune response when pathogens take longer to clear. The expression of 4-1BB on diverse cell types, evidence for bidirectional as well as receptor-independent signaling by 4-1BBL, the unexpected hyperproliferation of 4-1BB-deficient T cells, and complex effects of agonistic anti-4-1BB therapy have revealed additional roles for the 4-1BB/4-1BBL receptor/ligand pair in the immune system. In this review, we discuss these diverse roles of 4-1BB and its ligand in the immune response, exploring possible mechanisms for the observed complexities and implications for therapeutic applications of 4-1BB/4-1BBL. [source]

Gene expression characteristics of CD28null memory phenotype CD8+ T cells and its implication in T-cell aging

IMMUNOLOGICAL REVIEWS, Issue 1 2005
Monchou Fann
Summary:, Accumulation of CD28nullCD8+ T cells is considered as one of the hallmarks of aging in the human immune system. However, the precise changes of CD28nullCD8+ T cells, compared to those of the precursor CD28+CD8+ memory T cells, have not been determined. In this study, we present an analysis of the global gene expression profiles of CD28+ and CD28null memory phenotype CD8+ T cells. These two CD8+ T subsets exhibited an overall similar gene expression profile with only a few dozen genes that were differentially expressed. A wide range of functions, including co-stimulation, effector activity, signaling, and transcription, were possessed by these differentially expressed genes, reflecting significant functional changes of CD28null memory phenotype CD8+ T cells from their CD28+ counterparts. In addition, CD28null memory CD8+ T cells expressed several natural killer cell receptors and high levels of granzymes, perforin, and FasL, indicating an increasing capacity for cytotoxicity during memory CD8+ T-cell aging. Interestingly, in vitro culture of these two subsets with interleukin-15 showed that similar gene expression changes occurred in both subsets. Our analysis provides the gene expression portraits of CD28null memory phenotype CD8+ T cells and alteration from their CD28+ counterparts and suggests potential mechanisms of T-cell aging. [source]

Increased frequency of IFN-,-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis C

JOURNAL OF MEDICAL VIROLOGY, Issue 2 2002
Masayuki Murata
Abstract To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8+ T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-, (IFN-,), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-, after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-,-producing peripheral CD8+ T cells were found frequently in patients than in controls (P,<,0.05), whereas IL-4-producing peripheral CD8+ T cells were not. Although the frequency of peripheral CD28+CD8+ and CD28,CD8+ T cells in patients was not different from that of controls, CD28+CD8+ T cells exceeded CD28,CD8+ T cells in the capacity for IFN-,-production after mitogenic stimulation (P,<,0.01). In a more detailed analysis of the CD28+CD8+ T cells, CD45RA,CD28+CD8+ T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P,<,0.05). There were no significant correlations between the frequency of IFN-,-producing peripheral CD8+ T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8+ T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8+ T cells are associated with liver damage. J. Med. Virol. 67:162,170, 2002. © 2002 Wiley-Liss, Inc. [source]

An early commitment to expression of a particular TCRV, chain on CD8+ T cells responding to attenuated Plasmodium berghei sporozoites is maintained following challenge with infectious sporozoites

PARASITE IMMUNOLOGY, Issue 9-10 2010
J. M. LUMSDEN
Summary Protection induced by irradiated Plasmodium berghei sporozoites (Pb,-spz) in mice is linked to CD8+ T cells specific for exo-erythrocytic-stage Ags, and intrahepatic memory CD8+ T cells are associated with protracted protection. However, the Ag specificity of the protective CD8+ T cells remains largely unknown. In this study, we characterized the TCR V, usage by intrahepatic CD8+ T cells during ,-spz immunization and after the challenge with infectious Pb sporozoites. The repertoire of naïve (TN) and central memory (TCM) CD8+ T cells was diverse and conserved between individual mice, and did not change with immunization. In contrast, preferential usage of one or more TCR V, subset was observed in effector memory (TEM) CD8+ T cells after immunization. The expanded TCR V, varied between individual mice but V,4, 6, 7, 8.3, 9 and 11 were the most frequently expressed. In addition, there was a correlation in the TCR V, usage by ,-spz-induced CD8+ TEM in the liver and blood of individual mice. The expansion pattern of blood CD8+ TEM did not change with challenge and remained the same for 8 weeks thereafter. These results demonstrate that immunization with ,-spz skews the TCR V, repertoire of CD8+ TEM, and commitment to a particular TCR V, expression is maintained long-term. [source]