B Stockinger

..Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells...

..In order to avoid too many repetitions we focus this review mainly on publications in 2006 and 2007 and refer to a number of reviews, which cover earlier aspects of Th17/IL-17 biology...

..This was not because of a defect in T-cell homing to the tumor site or loss of MHC class II or costimulatory molecules by the tumor, but reflected mutual paralysis of T-cell responsiveness and antigen processing by tumor cells...

..Furthermore, the role of pathogens and pathogen-derived molecules in influencing effector T-cell polarization needs to be re-evaluated in the light of the differentiation conditions that favor Th17 T-cell responses...

..2007) examined the effects of interleukin-2 on differentiation of the T helper 17 (Th17) cells and found that this essential growth factor for all other T cell subsets blocks the development of Th17 T cells...

..Finally, we discuss a number of factors that affect long-term maintenance of memory CD4+ T cells...

..On the positive side, lymphopenia-provoked T cell expansion might enhance weak immune responses and thereby aid the rejection of tumours or the elimination of parasites...

..Here we discuss recent discoveries linking the development and functional potential of Th17 cells to a transcription factor that mediates the response to exogenous and endogenous environmental signals...

..The emerging picture is one of great versatility and functional heterogeneity as befits their central position within the immune system...

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..A number of recent reviews have highlighted potential new avenues of research. This review addresses recent new insight into physiological roles of AhR in the immune system...

..They differ qualitatively from naive T cells, suggesting that accelerated CD4 memory responses can occur without the need for increased frequencies of specific T cells...

..However, expression levels of Bcl-2 in either transgenic or polyclonal naive CD4 and CD8 T cells are similar, excluding a role for this molecule as a key factor in differential survival of CD4 vs CD8 T cells...

..These results are in line with recent observations that antagonistic signals direct differentiation into the CD8 lineage, regardless of MHC specificity...

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..Modulation of the CD49b-defined memory Th subsets may provide infection type-specific interventions, where either enhancement of the inflammatory response or reduction of immunopathology is essential...

..This indicates that endogenous T cell receptor rearrangements possibly leading to the expression of two receptors might be a prerequisite for their survival and export into the periphery...

..Their failure to present exogenous self Ag for negative selection suggests that macrophages concentrate on their primary function in the thymus, the disposal of dying thymocytes...

..In contrast to naive T cells, however, memory T cells can reach a homeostatic equilibrium, in which survival/self-renewal of each clone is dissociated from their avidity for MHC-derived signals...

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..This explains the failure to accumulate high numbers of peripheral T cells and suggests that the MHC-bound ligand(s) responsible for initiating survival signals is limiting for the selection and maintenance of A18 transgenic CD4 T cells...

..The data show that Ii41 fully substitutes for wild-type invariant chain in both positive and negative selection events during functional maturation of T cells with specificity for a natural, blood-borne self antigen...

..Despite the presence of these unidentified MHC class II ligands in the H-2(q) background and their potential influence on developing A18 thymocytes, however, MHC class I molecules were essential for thymic selection of A18 CD8 T cells...

..AHR ligands may therefore represent co-factors in the development of autoimmune diseases...

..Thus, memory T cells have a major role in the control of lymphopenia-induced proliferation of naive cells because they inhibit both the generation of memory-like T cells and their persistence within the memory compartment...

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..We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy...

..Furthermore, such intermittent activation during or after migration into extralymphoid sites could provide an important signal, promoting the survival and functional competence of memory T cells in the absence of Ag...

..It therefore seems unlikely that lymphopenia-induced proliferation of peripheral T cells causes deleterious side effects that result in immune pathology in states of partial and transient lymphopenia...

..Thus, in contrast to their survival, maintenance of the typical quality of memory T cells crucially depends on MHC-derived signals...

..Naïve T cells deficient in OX40 expression caused markedly reduced GVH in onset and severity despite some level of expansion in the adoptive host, suggesting an important role of this molecule in the immune pathology of GVHD...

..We show in this paper that B cell presentation in vitro induces a switch to the Th2 subset indicated by production of IL-4, and targetting C5 to B cells in vivo results in the generation of C5-specific antibodies...

..Although IL-10 is not required for in vitro suppression, it is vital for the in vivo function of regulatory T cells. Our data provide a link explaining the apparent difference in regulatory mechanisms in vitro and in vivo...

..As our data show, continued replenishment with cells from the thymus seems to be required to maintain efficient gut mucosal defense...

..Thus, transforming growth factor-beta constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways...

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..This suggests that up-regulation of negative T cell regulators in peripheral T cells exposed to chronic stimulation by Ag may prevent full functionality and thus avoid overt autoreactivity...

..Signals via AKT coordinate survival and metabolic pathways and may be one of the crucial events linking interaction with MHC class II molecules to the successful generation of a long-lived functional memory CD4 T cell population...

..Our data indicate that signals encountered by a naive T cell during its initial activation can profoundly influence its subsequent functional behavior and elicit T cells, which can have regulatory activity...

..These data show that TGF-beta is essential for the initiation of EAE and suggest that disease progression may require ongoing chronic inflammation and production of interleukin 23...

..An excess production of Th17 cells in response to infection or trauma could result in leakage into peripheral tissues and cause autoimmune pathology...

..These data show that Foxp3 expression is not a prerequisite for IL-10-T(Reg) activity in vitro or in vivo, and suggest that IL-10-T(Reg) and naturally occurring CD4(+)CD25(+) T(Reg) may have distinct origins...

..Thus, mutual interactions between DC and CD4+ T cell subpopulations following contact with pathogens are likely to influence the strength and quality of incipient immune responses in the local microenvironment...

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..Thus, CD8 T cells have access to the neuroendocrine system and get fully activated in the absence of CD4 help, but Ag recognition in this location causes autoimmune pathology only in the presence of excessive CD8 T cell numbers...

..We review here the different scenarios of homeostatic control mechanisms in steady state as well as severely or partially lymphopenic environments...

..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...

..Ag is cross-presented to host CD4(+) T cells on MHC class II and leads to the activation of Ag-specific effector T cells and clonal expansion in the draining lymph node...

..However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage...

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