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CD4 + CD25 high Foxp3 + regulatory T cells downregulate human Vδ2 + T‐lymphocyte function triggered by anti‐CD3 or phosphoantigen
Author(s) -
Mahan C. Scott,
Thomas Jeremy J.,
Boom W. Henry,
Rojas Roxana E.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02982.x
Subject(s) - il 2 receptor , antigen , t cell , biology , foxp3 , microbiology and biotechnology , t lymphocyte , cytotoxic t cell , immunology , t cell receptor , cd3 , cd8 , immune system , in vitro , biochemistry
Summary Vδ2 + T cells, the major circulating T‐cell receptor‐γδ‐positive (TCR‐γδ + ) T‐cell subset in healthy adults, are involved in immunity against many microbial pathogens including Mycobacterium tuberculosis . Vδ2 + T cells recognize small phosphorylated metabolites (phosphoantigens), expand in response to whole M. tuberculosis bacilli, and complement the protective functions of CD4 + T cells . CD4 + CD25 high Foxp3 + T cells (Tregs) comprise 5–10% of circulating T cells and are increased in patients with active tuberculosis (TB). We investigated whether, in addition to their known role in suppressing TCR‐αβ + lymphocytes, Tregs suppress Vδ2 + T‐cell function. We found that depletion of Tregs from peripheral blood mononuclear cells increased Vδ2 + T‐cell expansion in response to M. tuberculosis (H37Ra) in tuberculin‐skin‐test‐positive donors. We developed a suppression assay with fluorescence‐activated cell sorting‐purified Tregs and Vδ2 + T cells by coincubating the two cell types at a 1 : 1 ratio. The Tregs partially suppressed interferon‐γ secretion by Vδ2 + T cells in response to anti‐CD3 monoclonal antibody plus interleukin‐2 (IL‐2). In addition, Tregs downregulated the Vδ2 + T‐cell interferon‐γ responses induced by phosphoantigen (BrHPP) and IL‐2. Under the latter conditions there was no TCR stimulus for Tregs and therefore IL‐2 probably triggered suppressor activity. Addition of purified protein derivative (PPD) increased the suppression of Vδ2 + T cells, suggesting that PPD activated antigen‐specific Tregs. Our study provides evidence that Tregs suppress both anti‐CD3 and antigen‐driven Vδ2 + T‐cell activation. Antigen‐specific Tregs may therefore contribute to the Vδ2 + T‐cell functional deficiencies observed in TB.