DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory

被引：97

作者：

Lambe, Teresa ^{[1
]}

Crawford, Greg ^{[1
]}

Johnson, Andy L. ^{[1
]}

Crockford, Tanya L. ^{[1
]}

Bouriez-Jones, Tiphaine ^{[1
]}

Smyth, Aisling M. ^{[1
]}

Pham, Trung H. M. ^{[4
,5
]}

Zhang, Qian ^{[2
]}

Freeman, Alexandra F. ^{[3
]}

Cyster, Jason G. ^{[4
,5
]}

Su, Helen C. ^{[2
]}

Cornall, Richard J. ^{[1
]}

机构：

[1] Univ Oxford, Nuffield Dept Med, Oxford, England

[2] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA

[3] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

[4] UCSF, Howard Hughes Med Inst, San Francisco, CA 94143 USA

[5] UCSF, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2011年 / 41卷 / 12期

基金：

英国医学研究理事会;

关键词：

Human; Immunodeficiency; Memory; Rodent; T cells; WISKOTT-ALDRICH-SYNDROME; WHIM SYNDROME; LYMPHOCYTE MIGRATION; PROTEIN DOCK2; B-CELLS; GENERATION; MUTATIONS; EFFECTOR; NAIVE; DIFFERENTIATION;

D O I：

10.1002/eji.201141759

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 naive 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.

引用

页码：3423 / 3435

页数：13

共 48 条

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