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Essential Role for STAT5 Signaling in CD25⁺CD4⁺ Regulatory T Cell Homeostasis and the Maintenance of Self-Tolerance

Antov, Andrey and Yang, Lili and Vig, Monika and Baltimore, David and Van Parijs, Luk (2003) Essential Role for STAT5 Signaling in CD25⁺CD4⁺ Regulatory T Cell Homeostasis and the Maintenance of Self-Tolerance. Journal of Immunology, 171 (7). pp. 3435-3441. ISSN 0022-1767. https://resolver.caltech.edu/CaltechAUTHORS:20200417-142718273

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Abstract

A population of CD25⁺CD4⁺ regulatory T cells (T regs) functions to maintain immunological self tolerance by inhibiting autoreactive T cell responses. CD25⁺CD4⁺ T regs are present in low, but steady, numbers in the peripheral lymphoid tissues of healthy mice. Recent studies have shown that IL-2 is an essential growth factor for these cells. How this cytokine functions to regulate CD25⁺CD4⁺ T reg homeostasis and prevent autoimmune disease remains unknown. In conventional CD4⁺ T cells, IL-2 triggers signaling pathways that promote proliferation and survival by activating the STAT5 transcription factor and by increasing the expression of the antiapoptotic protein, Bcl-2. We show here that bcl-2 deficiency does not affect CD25⁺CD4⁺ T reg homeostasis, and that ectopic expression of this molecule fails to rescue CD25⁺CD4⁺ T reg numbers or to prevent the development of autoimmunity in IL-2-deficient mice. Furthermore, transient activation of STAT5 is sufficient to increase CD25⁺CD4⁺ T reg numbers in IL-2-deficient mice. Our study uncovers an essential role for STAT5 in maintaining CD25⁺CD4⁺ T reg homeostasis and self-tolerance.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.4049/jimmunol.171.7.3435DOIArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 2003 by The American Association of Immunologists. Received December 30, 2002. Accepted June 25, 2003. Published online September 19, 2003. This work was supported by a Career Development Award from the Juvenile Diabetes and Arthritis Foundation and a grant from the Broad Medical Research Foundation (to L.V.P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
Juvenile Diabetes and Arthritis FoundationUNSPECIFIED
Broad Medical Research FoundationUNSPECIFIED
Issue or Number:7
Record Number:CaltechAUTHORS:20200417-142718273
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200417-142718273
Official Citation:Essential Role for STAT5 Signaling in CD25+CD4+ Regulatory T Cell Homeostasis and the Maintenance of Self-Tolerance Andrey Antov, Lili Yang, Monika Vig, David Baltimore, Luk Van Parijs The Journal of Immunology October 1, 2003, 171 (7) 3435-3441; DOI: 10.4049/jimmunol.171.7.3435
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102636
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:20 Apr 2020 14:23
Last Modified:20 Apr 2020 14:23

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