IL-2, regulatory T cells, and tolerance.
IL-2 is a potent T cell growth factor that for many years was assumed to amplify lymphocyte responses in vivo. Accordingly, IL-2 has been used clinically to enhance T cell immunity in patients with AIDS or cancer, and blocking Abs to the IL-2R are used to inhibit T cell responses against transplanted tissues. It was later shown in mice that, unexpectedly, disruption of the IL-2 pathway results in lymphoid hyperplasia and autoimmunity rather than immune deficiency, indicating that the major physiological function of IL-2 is to limit rather than enhance T cell responses. This apparent paradox has recently been resolved with the discovery that IL-2 is critical for the development and peripheral expansion of CD4(+)CD25(+) regulatory T cells, which promote self-tolerance by suppressing T cell responses in vivo. Our new understanding of IL-2 biology prompts a re-evaluation of how best to clinically manipulate this important immunoregulatory pathway.
Nelson
Brad H
BH
Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada. bnelson@bccancer.bc.ca
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2