| First Author | Takada K | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 10 | Pages | 2253-69 |
| PubMed ID | 19752186 | Mgi Jnum | J:153506 |
| Mgi Id | MGI:4365653 | Doi | 10.1084/jem.20082553 |
| Citation | Takada K, et al. (2009) Self-class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels. J Exp Med 206(10):2253-69 |
| abstractText | Previous studies have suggested that naive CD8 T cells require self-peptide-major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide-MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels. |
