CD8+ suppressor T cells resurrected.
This review focuses on the role of antigen-specific T cells that mediate active inhibition of immune responses over the past 35 years since their initial description. The field has experienced several changes in the accepted paradigm of such suppressor/regulatory T cells, from initial indications that such cells were CD8(+), to the view that such cells did not exist, to the identification of the transcription factor Foxp3 as a key orchestrator of inhibitory function. Although most Foxp3(+) cells in a resting animal are CD4(+)CD25(+) cells, Foxp3 expression and inhibitory function can be induced by antigens in the periphery by selective cytokine conditions, particularly TGF-beta. Such induced T cells occur within both the CD4 and the CD8 T-cell lineages and appear to mediate suppression by inhibiting the costimulatory activity of antigen-presenting cells and the production of inhibitory cytokines. Recent data generated by analysis of TCR Tg T cells that do not select many Foxp3-positive cells during thymic development are reviewed, emphasizing the pattern of "linked suppression" and focus of the relative potency of different mechanisms of suppression.
Kapp
Judith A
JA
Department of Ophthalmology and Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. jkapp@uab.edu
Bucy
R Pat
RP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta