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CD4+CD25+Foxp3+ regulatory T cells maintain peripheral tolerance in the context of T cell LIP through preservation of TCR diversity
Author(s) -
Winstead Colleen Jean,
Khoruts Alex
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.848.23
Subject(s) - il 2 receptor , foxp3 , t cell receptor , immunology , immune system , biology , t cell , context (archaeology) , antigen , peripheral tolerance , regulatory t cell , immune tolerance , microbiology and biotechnology , paleontology
T cell diversity is a key feature of the adaptive immune system. Lymphopenia‐induced proliferation (LIP) can trigger oligoclonal expansion of T cells reacting to foreign or self‐antigens. This can result in loss of T cell diversity and compromise immune fitness that can be achieved following reconstitution by LIP. We demonstrate that CD4+CD25+Fopx3+ regulatory T cells selectively inhibit the spontaneous (fast) form of LIP, which is associated with differentiation into memory/effector‐like cells, and is likely to contain the most reactive T cell clones. Selective suppression of these clones is likely to leave more resources for T cells undergoing the slower homeostatic form of LIP. Putting it all together, we hypothesize that one of the functions of Tregs is to maintain the T cell diversity and overall immune fitness during reconstitution from lymphopenia. We are currently testing this hypothesis directly through flow cytometric analysis of TCR V beta usage, PCR‐based TCR J beta spectratyping, and sampling antigen‐specific cells by means of magnetic bead pull‐down with MHC class I and II tetramers.