Open AccessActivation of naturally occurring lung CD4+CD25+regulatory T cells requires CD8 and MHC I interaction
Author(s) -
Anthony Joetham,
Katsuyuki Takeda,
Nobuaki Miyahara,
Shigeki Matsubara,
Hiroshi Ohnishi,
Toshiyuki Koya,
Azzeddine Dakhama,
Erwin W. Gelfand
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0706765104
Subject(s) - il 2 receptor , cd8 , foxp3 , immunology , biology , adoptive cell transfer , mhc class i , microbiology and biotechnology , cytotoxic t cell , inflammation , t cell , antigen , immune system , in vitro , biochemistry
Naturally occurring Foxp3+ CD4+ CD25+ T cells (nTregs) isolated from lungs of naive mice regulate allergic airway hyperresponsiveness (AHR) and inflammation. Here, we demonstrate the critical requirement for engagement of MHC class I on CD4+ CD25+ T cells by CD8 for the functional activation of these nTregs. Suppression of allergen-induced AHR and inflammation by nTregs was abolished in mice treated with anti-CD8. Correspondingly, decreased levels of IL-10 and TGF-β and increased levels of Th2 cytokines in bronchoalveolar lavage were detected in these treated mice. Similarly, nTregs isolated from β2m−/− mice or from mice treated with anti-MHC I antibodyin vitro before intratracheal transfer failed to modulate AHR or inflammation. Coculture of nTregs with CD8+ T cells increased IL-10 and TGF-β. Addition of anti-MHC I or anti-CD8 reduced IL-10 and TGF-β. These results demonstrate that functional activation of nTregs requires the interaction between MHC I on CD4+ CD25+ T cells and CD8.