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Publication : Activation of naturally occurring lung CD4(+)CD25(+) regulatory T cells requires CD8 and MHC I interaction.

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.
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