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In vitro induction of CD25 + CD4 + regulatory T cells by the neuropeptide alpha‐melanocyte stimulating hormone (α‐MSH)
Author(s) -
Taylor AW,
Namba K
Publication year - 2001
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2001.01022.x
Subject(s) - il 2 receptor , lymphokine , interleukin 21 , biology , cytotoxic t cell , population , cytokine , microbiology and biotechnology , natural killer t cell , interleukin 3 , effector , antigen , in vitro , medicine , immunology , biochemistry , environmental health
Recently, we have found that the neuropeptide alpha‐melanocyte stimulating hormone (α‐MSH) not only suppresses IFN‐γ production, but also induces TGF‐β1 production by activated effector T cells. These α‐MSH‐ treated effector T cells function as regulatory T cells in that they suppress IFN‐γ production and hypersensitivity mediated by other effector T cells. Experimental autoimmune uveoretinitis (EAU) was suppressed in its severity and incidence in mice that were injected with primed T cells activated in vitro by APC and antigen in the presence of α‐MSH. Moreover, it appeared that α‐MSH had converted a population of effector T cells polarized to mediate hypersensitivity into a population of T cells that now mediated immunoregulation. To characterize these α‐MSH‐ treated T cells, primed T cells were TCR‐stimulated in the presence of α‐MSH in vitro and their lymphokine profile was examined. Such effector T cells displayed enhanced levels of TGF‐β1 production and no IFN‐γ or IL‐10, with IL‐4 levels remaining unchanged in comparison with inactivated T cells. In addition, if soluble TGF‐β receptor II was added to cocultures of α‐MSH‐treated T cells and activated Th1 cells, the α‐MSH‐treated T cells could not suppress IFN‐γ production by the Th1 cells. These results suggest that α‐MSH induces T cells with a regulatory lymphokine pattern, and that through their production of TGF‐β1 these cells suppress other effector T cells. Examination of the α‐MSH‐treated T cells showed that α‐MSH did not alter the phosphorylation of CD3 molecules following TCR engagement. Primed T cells express the melanocortin 5 receptor (MC5r), a receptor that is linked to an intracellular signalling pathway shared by other cytokine receptors. Blocking the receptor with antibody prevented α‐MSH from suppressing IFN‐γ production by the activated regulatory T cells, suggesting that α‐MSH immunoregulation is through the MC5r on primed T cells. Surface staining and cell sorting of the α‐MSH‐ treated primed T cells showed that the regulatory T cells are CD25 + CD4 + T cells. From these results we find that α‐MSH can mediate the induction of CD25 + CD4 + regulatory T cells. These regulatory T cells require specific antigen for activation, but through non‐specific TGF‐β1‐mediated mechanisms they can suppress other effector T cells.