Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1084/jem.20110345

Type

Journal article

Journal

J Exp Med

Publication Date

24/10/2011

Volume

208

Pages

2305 - 2320

Keywords

Animals, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Division, Cell Proliferation, Cell Survival, Guanine Nucleotide Exchange Factors, Humans, Immunologic Deficiency Syndromes, Immunologic Memory, Immunological Synapses, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Orthomyxoviridae, Phenotype, Transplantation Chimera