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, Erwin W. Gelfand

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)15057-15062
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
Publication statusPublished - Sep 18 2007
Externally publishedYes


  • Airway reactivity
  • IL-10
  • TGF-β

ASJC Scopus subject areas

  • General


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