Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Deficiency in the guanine nucleotide exchange factor dedicator of cytokinesis 8 (DOCK8) causes a human immunodeficiency syndrome associated with recurrent sinopulmonary and viral infections. We have recently identified a DOCK8-deficient mouse strain, carrying an ethylnitrosourea-induced splice-site mutation that shows a failure to mature a humoral immune response due to the loss of germinal centre B cells. In this study, we turned to T-cell immunity to investigate further the human immunodeficiency syndrome and its association with decreased peripheral CD4(+) and CD8(+) T cells. Characterisation of the DOCK8-deficient mouse revealed T-cell lymphopenia, with increased T-cell turnover and decreased survival. Egress of mature CD4(+) thymocytes was reduced with increased migration of these cells to the chemokine CXCL12. However, despite the two-fold reduction in peripheral naïve T cells, the DOCK8-deficient mice generated a normal primary CD8(+) immune response and were able to survive acute influenza virus infection. The limiting effect of DOCK8 was in the normal survival of CD8(+) memory T cells after infection. These findings help to explain why DOCK8-deficient patients are susceptible to recurrent infections and provide new insights into how T-cell memory is sustained.

Original publication

DOI

10.1002/eji.201141759

Type

Journal article

Journal

Eur J Immunol

Publication Date

12/2011

Volume

41

Pages

3423 - 3435

Keywords

Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Movement, Cell Survival, Cells, Cultured, Chemokine CXCL12, Guanine Nucleotide Exchange Factors, Humans, Immunologic Deficiency Syndromes, Immunologic Memory, Lymphocyte Activation, Lymphoma, T-Cell, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections