title: The molecular mechanisms of regulatory T cell immunosuppression.
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.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA. ppandiyan@niaid.nih.gov
authors.forename: Pushpa
authors.initials: P
authors.lastname: Pandiyan
authors.forename: Lixin
authors.initials: L
authors.lastname: Zheng
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo