First Author | Joetham A | Year | 2007 |
Journal | Proc Natl Acad Sci U S A | Volume | 104 |
Issue | 38 | Pages | 15057-62 |
PubMed ID | 17855564 | Mgi Jnum | J:125195 |
Mgi Id | MGI:3757821 | Doi | 10.1073/pnas.0706765104 |
Citation | Joetham A, et al. (2007) Activation of naturally occurring lung CD4+CD25+ regulatory T cells requires CD8 and MHC I interaction. Proc Natl Acad Sci U S A 104(38):15057-62 |
abstractText | 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-beta and increased levels of Th2 cytokines in bronchoalveolar lavage were detected in these treated mice. Similarly, nTregs isolated from beta2m(-/-) 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-beta. Addition of anti-MHC I or anti-CD8 reduced IL-10 and TGF-beta. These results demonstrate that functional activation of nTregs requires the interaction between MHC I on CD4(+)CD25(+) T cells and CD8. |