| First Author | Do JS | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 31 | Pages | 12698-703 |
| PubMed ID | 22802622 | Mgi Jnum | J:188517 |
| Mgi Id | MGI:5440800 | Doi | 10.1073/pnas.1207219109 |
| Citation | Do JS, et al. (2012) Unexpected role for MHC II-peptide complexes in shaping CD8 T-cell expansion and differentiation in vivo. Proc Natl Acad Sci U S A 109(31):12698-703 |
| abstractText | Here we report a unique role for MHC II-peptide complexes in controlling immune responses of naive CD8 T cells. Compared with CD8 T cells from WT mice, CD8 T cells isolated from MHC II(-/-) mice hyperproliferated under lymphopenic conditions, differentiated into effector cells producing proinflammatory cytokines, and mediated more severe tissue inflammation. The elevated responses of MHC II(-/-) CD8 T cells were due to the absence of MHC II, but not CD4, T cells. The hyperreactivity appeared to be a feature of mature T cells, given its absence in CD8 single positive thymocytes derived from MHC II(-/-) mice. Expression of the MHC II ligand LAG3 was markedly enhanced during in vivo activation of MHC II(-/-) CD8 T cells, and blockade of MHC II-LAG3 interactions further enhanced T-cell expansion. Importantly, CD8 T cells isolated from H-2M(-/-) mice expressing WT levels of MHC II also displayed hyperresponsiveness similar to that of MHC II(-/-) CD8 T cells, suggesting that peptides presented on MHC II are involved in the control of CD8 T-cell responses. Our results uncover a previously undefined MHC II-dependent regulation that tunes CD8 T-cell reactivity and may have implications for an improved understanding of CD8 T-cell homeostasis and functions. |
