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Cell Help (cell + help)
Kinds of Cell Help Selected AbstractsCD4+ T cell help improves CD8+ T cell memory by retained CD27 expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Matthias 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] Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: Implications for vaccination of immunocompromised individualsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Corey Smith Abstract Studies based on either MHC class II-knockout or CD4+ T cell-depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, we have developed a model setting, which allows studies on the generation of CD8+ T cell memory responses in a transient CD4+ T cell-deficient setting similar to that seen in immunocompromised patients. Immunisation with an adenoviral vaccine under transient helpless or help-deficient conditions showed varying degrees of impact on the priming of CD8+ T cell responses. Antigen-specific T cells generated under normal CD4+ T cell help and transient help-deficient conditions showed similar effector phenotype and were capable of proliferation upon secondary antigen encounter. Most importantly, in spite of CD4+ T cell deficiency, the long-term CD8+ T cell memory response remained functionally stable and showed comparable cytotoxic effector function as seen in CD8+ T cells generated with normal CD4+ T cell numbers. These findings provide evidence that in spite of partially impaired activation of a primary CD8+ T cell response, a fully functional and stable memory CTL response can be induced under conditions of severe transient CD4+ T cell deficiency. [source] The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Simmi Mahajan Abstract We have addressed the role of the inducible costimulator (ICOS) in the development of T cell help for B cells and in the generation, survival and reactivation of memory CD4 T cells and B cells. We find that while T cell help for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS-KO) mice, the IFN-, response is little affected, indicating a defect in helper function that is unrelated to cytokine production. In addition, the ICOS-negative T cells do not accumulate in B cell follicles. Secondary (memory), but not primary, clonal proliferation of antigen-specific B cells is impaired in ICOS-KO mice, as is the generation of secondary antibody-secreting cells. Analysis of endogenous CD4 memory cells in ICOS-KO mice, using MHC class,II tetramers, reveals normal primary clonal expansion, formation of memory clones and long-term (10,wk) survival of memory cells, but defective expansion upon reactivation in vivo. The data point to a role of ICOS in supporting secondary, memory and effector T cell responses, possibly by influencing cell survival. The data also highlight differences in ICOS dependency of endogenous T cell proliferation in vivo compared to that of adoptively transferred TCR-transgenic T cells. [source] CD4+CD25+ regulatory T,cells control the magnitude ofT-dependent humoral immune responses to exogenous antigensEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Fouad Eddahri Abstract CD4+CD25+ T,reg cells are critical for peripheral tolerance and prevention of autoimmunity. Here we show that CD4+CD25+ T,reg also regulate the magnitude of humoral responses against a panel of T-dependent antigens of foreign origin during both primary and secondary immune responses. Depletion of CD4+CD25+ T,cells leads to increased antigen-specific antibody production and affinity maturation but does not affect T-independent B,cell responses, suggesting that CD4+CD25+ T,reg exert a feedback mechanism on non-self antigen-specific antibody secretion by dampening the T,cell help for B,cell activation. Moreover, we show that CD4+CD25+ T,reg also suppress in vitro B,cell immunoglobulin production by inhibiting CD4+CD25, T,cell help delivery, and that blockade of TGF-, activity abolishes this suppression. [source] Altered primary CD8+ T,cell response to a modified virus Ankara(MVA)-vectored vaccine in the absence of CD4+ T,cell helpEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Marie Abstract T,cell receptor-transgenic F5 mice were used to assess primary CD8+ T,cell responses to a modified virus Ankara (MVA)-vectored vaccine in the absence of CD4+ T,cell help. Naive, CD8-enriched, CFSE-labelled F5 cells were transferred into normal or CD4+ cell-depleted mice and the mice were vaccinated with MVA.HIVA-NP. At different time points during the primary response, F5 cells were re-isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8+ T,cell response in the absence of CD4+ T,cell help differed from that in normal CD4+ cell-undepleted mice. While in the absence of CD4+ T,cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8+ T,cell memory after contraction. T,cells primed without help displayed accelerated proliferation and activation, while expression of interferon-, remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA-NP immunization site and were similar, but delayed by 2,3,days in spleen and non-draining lymph nodes. [source] CD4 T cells guarantee optimal competitive fitness of CD8 memory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2004Pål Johansen Abstract We studied the contribution of CD4 T cell help to survival and competitive fitness of CD8 memory T cells specific for influenza virus nucleoprotein. In agreement with recent studies, the optimal generation of functional memory CD8 T cells required CD4 help, although long-term maintenance of resting CD8 memory T cells did not absolutely depend on the presence of CD4 T cells. Nonetheless, CD4 T cells were essential during differentiation of CD8 memory T cells to imprint on them the capacity to compete effectively with other memory T cells. CD8 memory cells generated with help survived better in secondary polyclonal hosts, and co-transfer into lymphopenic hosts together with "un-helped" CD8 memory cells showed improved homeostatic expansion of CD8 memory cells that had been generated with CD4 help. Therefore, the requirement for CD4 help in CD8 T cell memory extends to homeostatic parameters that ensure the maintenance and competitive fitness of memory clones. [source] B Cells Help Alloreactive T Cells Differentiate Into Memory T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010Y.-H. Ng B cells are recognized as effector cells in allograft rejection that are dependent upon T cell help to produce alloantibodies causing graft injury. It is not known if B cells can also help T cells differentiate into memory cells in the alloimmune response. We found that in B-cell-deficient hosts, differentiation of alloreactive T cells into effectors was intact whereas their development into memory T cells was impaired. To test if B cell help for T cells was required for their continued differentiation into memory T cells, activated T cells were sorted from alloimmunized mice and transferred either with or without B cells into naïve adoptive hosts. Activated T cells cotransferred with B cells gave rise to more memory T cells than those transferred without B cells and upon recall, mediated accelerated rejection of skin allografts. Cotransfer of B cells led to increased memory T cells by enhancing activated CD4 T-cell proliferation and activated CD8 T-cell survival. These results indicate that B cells help alloreactive T-cell differentiation, proliferation and survival to generate optimal numbers of functional memory T cells. [source] Virus-specific CD8 T cells: activation, differentiation and memory formationAPMIS, Issue 5-6 2009MELANIE WIESEL CD8 T cells are pivotal for the control of many intracellular pathogens, and besides their role in immediate control of infections, CD8 T cells have the capacity to differentiate into long-lived antigen-independent memory CD8 T cells, at least in situations of acute and resolved infections. The population of memory cells is heterogeneous with respect to their phenotype, their anatomical localization and their functional capacities in order to afford optimal protection against secondary infections. In the past years, it has become clear that multiple in vivo parameters are involved in shaping the composition of the memory CD8 T cell population, including antigen load, duration and strength of CD8 T cell stimulation, the level of inflammation, availability of CD4 T cell help and CD8 T cell precursor frequencies. With respect to the timing when CD8 T cells are committed to become memory cells, several models have been proposed. In contrast to acute, resolved infection, the continued in vivo exposure to high levels of antigen during persistent chronic viral infection precludes the development of long-lived antigen-independent memory CD8 T cells and might even result in severe dysfunction of virus-specific CD8 T cells. [source] Autoimmune regulator controls T cell help for pathogenetic autoantibody production in collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2009Ian K. Campbell Objective Autoimmune regulator (Aire) promotes the ectopic expression of tissue-restricted antigens in medullary thymic epithelial cells (mTECs), leading to negative selection of autoreactive T cells. This study was undertaken to determine whether loss of central tolerance renders Aire-deficient (Aire,/,) mice more susceptible to the induction of autoimmune arthritis. Methods Medullary TECs were isolated from Aire,/, and wild-type C57BL/6 mice for gene expression analysis. Collagen-induced arthritis (CIA) was elicited by injection of chick type II collagen (CII) in adjuvant. Cellular and humoral immune responses to CII were evaluated. Chimeric mice were created by reconstituting lymphocyte-deficient mice with either Aire,/, or wild-type CD4 T cells and wild-type B cells. Results Wild-type, but not Aire,/,, mTECs expressed the CII gene Col2a1. Aire,/, mice developed more rapid and severe CIA, showing elevated serum anti-CII IgG levels, with earlier switching to arthritogenic IgG subclasses. No evidence was found of enhanced T cell responsiveness to CII in Aire,/, mice; however, Aire,/, CD4 T cells were more efficient at stimulating wild-type B cells to produce anti-CII IgG following immunization of chimeric mice with CII. Conclusion Our findings indicate that Aire-dependent expression of CII occurs in mTECs, implying that there is central tolerance to self antigens found in articular cartilage. Reduced central tolerance to CII in Aire,/, mice manifests as increased CD4 T cell help to B cells for cross-reactive autoantibody production and enhanced CIA. Aire and central tolerance help prevent cross-reactive autoimmune responses to CII initiated by environmental stimuli and limit spontaneous autoimmunity. [source] Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivityCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2010M. Focke Summary Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment. Cite this as: M. Focke, I. Swoboda, K. Marth and R. Valenta, Clinical & Experimental Allergy, 2010 (40) 385,397. [source] | ||||||||||