Function of the IL-2R for thymic and peripheral CD4+CD25+ Foxp3+ T regulatory cells.
IL-2 contributes to the production, function, and homeostasis of CD4+CD25+ T(reg) cells. However, it remains uncertain whether IL-2 is essential for the development of T(reg) cells in the thymus, their homeostasis in the periphery, or both. The present study was undertaken to investigate the contribution of IL-2 during thymic T(reg) cell development and its maintenance in peripheral immune tissue. Relying on genetic mouse models where IL-2R signaling was either completely blocked or selectively inhibited in peripheral CD4+CD25+ T(reg) cells, we show that the IL-2/IL-2R interaction is active in the thymus at the earliest stage of the development of T(reg) cells to promote their expansion and to up-regulate Foxp3 and CD25 to normal levels. Furthermore, CD4+CD25+Foxp3+ T(reg) cells with impaired IL-2-induced signaling persist in the periphery and control autoimmunity without constant thymic output. These peripheral T(reg) cells with poor responsiveness to IL-2 exhibited slower growth and extended survival in vivo, somewhat lower suppressive activity, and poor IL-2-dependent survival in vitro. Mixed thymic and bone marrow chimeric mice showed that wild-type-derived T(reg) cells were substantially more effective in populating peripheral immune tissue than T(reg) cells with impaired IL-2 signaling. Collectively, these data support the notion that normally IL-2 is a dominant mechanism controlling the number of thymic and peripheral T(reg) cells.
Bayer
Allison L
AL
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, 1600 Northwest 10th Avenue, Miami, FL 33136, USA.
Yu
Aixin
A
Malek
Thomas R
TR
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D015375:Receptors, Interleukin-2