Ever since Regulatory T cells (T-Regs) were first defined as peripheral CD4+ T cells that express the interleukin-2 (IL-2) receptor alpha chain (IL-2Rα), there have been intensive efforts to determine the molecular mechanisms whereby this minor subset of CD4+ T cells (~ 5-10%) nonspecifically suppresses all potential effector T cells, whether reactive to self or non-self antigens. Multiple possible molecular mechanisms have been implicated, including the scavenging of IL-2 via the expression of high densities of IL-2Rs, the inhibition of antigen presentation via CTLA-4 molecules leading to decreased IL-2 production, the activation of intracellular cAMP thereby suppressing both IL-2 production and action, and the production of suppressive cytokines such as IL-10 and Tumor Growth Factor-beta, to list a few. However, the field has thus far failed to come to a consensus, such that some investigators have now asserted that many molecular mechanisms may be operative, in fact that perhaps all of the described mechanisms may account for the suppressive effects of these cells, acting either simultaneously or sequentially. Thus, this Research Topic is focused on articles that can shed some new light on the molecular mechanisms responsible for T-Reg immunosuppression.
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