| First Author | Randall KL | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 11 | Pages | 2305-20 |
| PubMed ID | 22006977 | Mgi Jnum | J:178763 |
| Mgi Id | MGI:5300105 | Doi | 10.1084/jem.20110345 |
| Citation | Randall KL, et al. (2011) DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. J Exp Med 208(11):2305-20 |
| abstractText | In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA(+)CCR7(-) phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells. |
