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The role of the combination of IL‐2 and TGF‐β or IL‐10 in the generation and function of CD4 + CD25 + and CD8 + regulatory T cell subsets
Author(s) -
Horwitz David A.,
Zheng Song Guo,
Gray J. Dixon
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0503228
Subject(s) - il 2 receptor , biology , regulatory t cell , cd8 , cytotoxic t cell , t cell , cytokine , interleukin 21 , microbiology and biotechnology , interleukin 10 , immunology , immune system , in vitro , biochemistry
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.