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1: J Exp Med. 2008 Sep 1;205(9):1975-81. Epub 2008 Aug 18.
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CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner.

Andersson J, Tran DQ, Pesu M, Davidson TS, Ramsey H, O'Shea JJ, Shevach EM.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

CD4(+)FoxP3(+) regulatory T (T reg) cells comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. The molecular mechanism(s) by which T reg cells mediate their suppressive effects remains poorly understood. One molecule that has been extensively studied in T reg cell suppression is transforming growth factor (TGF)-beta, but its importance remains controversial. We found that TGF-beta complexed to latency-associated peptide (LAP) is expressed on the cell surface of activated but not resting T reg cells. T reg cell LAP-TGF-beta plays an important role in the suppression of the proliferation of activated T cells, but it is not required for the suppression of naive T cell activation. More importantly, T reg cell-derived TGF-beta could generate de novo CD4(+)FoxP3(+) T cells in vitro from naive precursors in a cell contact-dependent, antigen-presenting cell-independent and alpha(V) integrin-independent manner. The newly induced CD4(+)FoxP3(+) T cells are suppressive both in vitro and in vivo. Transfer of activated antigen-specific T reg cells with naive antigen-specific responder T cells to normal recipients, followed by immunization, also results in induction of FoxP3 expression in the responder cells. T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities.

Publication Types:
PMID: 18710931 [PubMed - indexed for MEDLINE]

PMCID: PMC2526184 [Available on 03/01/09]