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.
Original language | English |
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Pages (from-to) | 15057-15062 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Issue number | 38 |
DOIs | |
Publication status | Published - Sep 18 2007 |
Externally published | Yes |
Keywords
- Airway reactivity
- IL-10
- TGF-β
ASJC Scopus subject areas
- General