AUTHOR=Pandiyan Pushpa , Zheng Lixin , Lenardo Michael TITLE=The Molecular Mechanisms of Regulatory T Cell Immunosuppression JOURNAL=Frontiers in Immunology VOLUME=2 YEAR=2011 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2011.00060 DOI=10.3389/fimmu.2011.00060 ISSN=1664-3224 ABSTRACT=

CD4⁺CD25⁺Foxp3⁺ T lymphocytes, known as regulatory T cells or T_regs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective “helper” and “cytotoxic” lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of T_regs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4⁺ effector T cells are directly inhibited by T_regs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion; and 4. Contrary to the current view, we discuss new evidence that T_regs, similar to other T-cells lineages, can promote protective immune responses in certain infectious contexts (Chen et al., 2011; Pandiyan et al., 2011). Although these points are at variance to varying degrees with the standard model of T_reg behavior, we will recount developing findings that support these new concepts.