Recently, considerable attention has been focused on thymus-derived CD4+ regulatory T cells that constitutively express CD25 and have a contact-dependent, cytokine-independent mechanism in vitro. However, peripheral CD4+ and CD8+ T cells can also be induced to become regulatory T cells. Here we review our studies using the combination of IL-2 and transforming growth factor β (TGF-β) to generate regulatory T cell subsets ex vivo, and the work of others using IL-10 to induce suppressive activity. Under certain conditions, the autocrine effects of TGF-β and IL-10 induce peripheral T cells to produce immunosuppressive levels of each of these cytokines. This effect of TGF-β is IL-2 dependent. Under other conditions IL-2 and TGF-β can induce CD4+ cells to develop potent contact-dependent, cytokine-independent regulatory activity. At present, there is considerable confusion concerning the mechanism of action of CD4 + CD25+ cells because cytokine-producing regulatory T cells generated in the periphery can express CD25 and other markers displayed by naturally occurring, thymus-derived regulatory T cells. We, therefore, propose a nomenclature that identifies thymus-derived and peripheral regulatory cells, and that also differentiates T regulatory cells from T helper cells. Because T regulatory cells broadly control T helper cell reactivity, the mechanisms that control regulatory cell function are also reviewed. Finally, the potential use of regulatory T cells generated ex vivo as an adoptive immunotherapy for certain autoimmune diseases, to prevent organ graft rejection, or to prevent pathologic host responses to infectious agents is discussed.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cell Biology