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Induction of CD4 + CD25 + Foxp3 − regulatory T cells by Thy‐1 stimulation of CD4 + T cells
Author(s) -
Conrad David M,
Coombs Melanie R Power,
Furlong Suzanne J,
Forward Nicholas A,
Hoskin David W
Publication year - 2012
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 - 10.1038/icb.2011.33
Subject(s) - il 2 receptor , microbiology and biotechnology , t cell , interleukin 21 , biology , interleukin 12 , cytotoxic t cell , chemistry , in vitro , immunology , immune system , biochemistry
Thy‐1 (CD90) on mouse T cells has been reported to have both T‐cell activating and regulatory roles. In this study, we show that monoclonal antibody (mAb)‐mediated crosslinking of Thy‐1 on CD4 + mouse T‐cells‐induced regulatory T (T reg ) cells that expressed CD25, CD39 and glucocorticoid‐induced tumor necrosis factor receptor family‐related gene, but not CD73, CD122 or Foxp3. The proliferation of CD4 + T responder cells in response to anti‐CD3/anti‐CD28mAb‐coated T‐cell expander beads or syngeneic dendritic cells and soluble anti‐CD3mAb was inhibited by Thy‐1‐induced T reg cells, in spite of elevated IL‐2 levels in the co‐cultures. Interestingly, stimulation with T‐cell expander beads caused Thy‐1‐induced T reg cells to synthesize large amounts of interleukin‐2 (IL‐2). IL‐10 was also elevated in co‐cultures of activated T responder cells and Thy‐1‐induced T reg cells. However, mAb‐mediated neutralization of IL‐10 did not restore T responder ‐cell proliferation to control levels, which excluded IL‐10 as a potential mediator of Thy‐1‐induced T reg ‐cell suppressor function. In addition, Thy‐1‐induced T reg cells did not inhibit IL‐2‐dependent proliferation of CTLL‐2 cells, suggesting that IL‐2 receptor signaling remained intact in the presence of Thy‐1‐induced T reg cells. We suggest that T reg cells induced by Thy‐1 ligation in vivo may contribute to the maintenance of T‐cell homeostasis.