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Blood monocytes, myeloid dendritic cells and the cytokines interleukin (IL)‐7 and IL‐15 maintain human CD4 + T memory cells with mixed helper/regulatory function *
Author(s) -
McKinlay Adam,
Radford Kristen,
Kato Masato,
Field Ken,
Gardiner Damien,
Khalil Dalia,
Burnell Fiona,
Hart Derek,
Vuckovic Slavica
Publication year - 2007
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.1365-2567.2006.02515.x
Subject(s) - immunology , dendritic cell , antigen presenting cell , t cell , biology , microbiology and biotechnology , interleukin 21 , monocyte , myeloid , interleukin 3 , memory t cell , chemistry , antigen , immune system
Summary The number and function of human T cells in the periphery are regulated by homeostatic signals received from antigen‐presenting cells (APCs) and the common gamma chain (γc) cytokines interleukin (IL)‐7 and IL‐15. We found that, in the absence of introduced antigen, blood monocytes or myeloid dendritic cells (MDCs) in the presence of IL‐7 and IL‐15 (IL‐7/IL‐15) can regulate CD4 + T memory (Tm) cell numbers by polyclonal cell proliferation. The dynamics of CD4 + Tm cell proliferation, in the presence of IL‐7/IL‐15, was dependent on contact with MDCs and to a lesser extent on contact with monocytes. IL‐7/IL‐15 either alone or combined with monocytes or MDCs enhanced the proportion of CD4 + Tm cells with activated and effector phenotype and diminished the helper function of CD4 + Tm cells. These CD4 + Tm cells, preconditioned with IL‐7/IL‐15 alone or with monocytes or MDCs and IL‐7/IL‐15, reduced T cell‐dependent immunoglobulin M (IgM) and IgG responses. This appeared to be a contact‐dependent effect involving a reduction in antibody‐producing CD27 + B memory cells, but contact‐independent suppression by soluble factors also contributed to the antibody‐producing capacity of CD27 + B memory cells. These results indicate that blood monocytes, MDCs and the cytokines IL‐7/IL‐15 contribute to homeostasis of CD4 + Tm cells by regulating their number, activation state and helper/suppressor (regulatory) function. In healthy individuals, this mode of regulating CD4 + Tm cell homeostasis may provide a basis for the control of autoimmune responses.