Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function.
CD4(+)CD25(+) T cells are potent immunoregulatory cells that suppress TCR-induced proliferation of CD4 and CD8 T cells in vitro by a cell contact-dependent mechanism. Addition of IL-2 or anti-CD28 abrogates CD4(+)CD25(+)-mediated suppression of proliferation and has been assumed to "break suppression." We examined IL-2 mRNA by quantitative PCR in cocultures of mouse CD4(+)CD25(+) and CD4(+)CD25(-) T cells. Although IL-2 gene transcription was inhibited in the presence or absence of exogenous IL-2, the addition of anti-CD28 stimulated endogenous IL-2 production. Surprisingly, transcription of IL-2 mRNA was also restored in the cocultures in the presence of anti-IL-2. These results are most compatible with a model in which CD4(+)CD25(+) T cells do not suppress the initial activation of CD4(+)CD25(-) T cells, but mediate their suppressive effects following production of IL-2 by the responder cells resulting in both the expansion of the CD4(+)CD25(+) T cells and the induction of their suppressor function.
Thornton
Angela M
AM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. athornton@niaid.nih.gov
Donovan
Erin E
EE
Piccirillo
Ciriaco A
CA
Shevach
Ethan M
EM
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D005260:Female; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D018106:CD28 Antigens; D015704:CD4 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2