Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells

Both naturally arising Foxp3(+) and antigen-induced Foxp3(-) regulatory T cells (Treg) play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pat...

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Veröffentlicht in:PloS one 2009-11, Vol.4 (11), p.e7863-e7863
Hauptverfasser: Chen, Cyndi, Liu, Chih-Pin
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Sprache:eng
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Zusammenfassung:Both naturally arising Foxp3(+) and antigen-induced Foxp3(-) regulatory T cells (Treg) play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. Using a novel class II MHC tetramer, we have isolated a population of CD4(+) Foxp3(-) T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells) from diabetes-resistant non-obese resistant (NOR) mice. These Foxp3(-) NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. These studies identified a unique population of autoantigen-specific Foxp3(-) Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0007863