Activation of naturally occurring lung CD4+CD25+ regulatory T cells requires CD8 and MHC I interaction
- Anthony Joetham,
- Katsuyuki Takeda,
- Nobuaki Miyahara,
- Shigeki Matsubara,
- Hiroshi Ohnishi,
- Toshiyuki Koya,
- Azzeddine Dakhama, and
- Erwin W. Gelfand*
- Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206
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Communicated by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, July 24, 2007 (received for review April 4, 2007)
Abstract
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 antibody in 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.
Footnotes
- *To whom correspondence should be addressed. E-mail: gelfande{at}njc.org
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Author contributions: A.J., K.T., and E.W.G. designed research; A.J., K.T., N.M., S.M., H.O., and T.K. performed research; A.J. and E.W.G. analyzed data; and A.J., A.D., and E.W.G. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0706765104/DC1.
- Abbreviations:
- AHR,
- airway hyperresponsiveness;
- Treg,
- regulatory T cell;
- nTreg,
- naturally occurring regulatory T cell;
- BAL,
- bronchoalveolar lavage;
- NK,
- natural killer;
- β2m−/−,
- β2-microglobulin-deficient;
- OVA,
- ovalbumin.
- © 2007 by The National Academy of Sciences of the USA
