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

Teresa Lambe, Greg Crawford, Andy L. Johnson, Tanya L. Crockford, Tiphaine Bouriez-Jones, Aisling M. Smyth, Trung H M Pham, Qian Zhang, Alexandra F. Freeman, Jason G. Cyster, Helen C. Su, Richard J. Cornall

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)3423-3435
Number of pages13
JournalEuropean Journal of Immunology
Volume41
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Cytokinesis
Cell Survival
Maintenance
T-Lymphocytes
Virus Diseases
Ethylnitrosourea
Guanine Nucleotide Exchange Factors
Chemokine CXCL12
Lymphopenia
Germinal Center
Survival
Thymocytes
Humoral Immunity
Infection
Orthomyxoviridae
Cell Movement
Immunity
B-Lymphocytes
Mutation

Keywords

  • Human
  • Immunodeficiency
  • Memory
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Lambe, T., Crawford, G., Johnson, A. L., Crockford, T. L., Bouriez-Jones, T., Smyth, A. M., ... Cornall, R. J. (2011). DOCK8 is essential for T-cell survival and the maintenance of CD8 + T-cell memory. European Journal of Immunology, 41(12), 3423-3435. https://doi.org/10.1002/eji.201141759

DOCK8 is essential for T-cell survival and the maintenance of CD8 + T-cell memory. / Lambe, Teresa; Crawford, Greg; Johnson, Andy L.; Crockford, Tanya L.; Bouriez-Jones, Tiphaine; Smyth, Aisling M.; Pham, Trung H M; Zhang, Qian; Freeman, Alexandra F.; Cyster, Jason G.; Su, Helen C.; Cornall, Richard J.

In: European Journal of Immunology, Vol. 41, No. 12, 12.2011, p. 3423-3435.

Research output: Contribution to journalArticle

Lambe, T, Crawford, G, Johnson, AL, Crockford, TL, Bouriez-Jones, T, Smyth, AM, Pham, THM, Zhang, Q, Freeman, AF, Cyster, JG, Su, HC & Cornall, RJ 2011, 'DOCK8 is essential for T-cell survival and the maintenance of CD8 + T-cell memory', European Journal of Immunology, vol. 41, no. 12, pp. 3423-3435. https://doi.org/10.1002/eji.201141759
Lambe T, Crawford G, Johnson AL, Crockford TL, Bouriez-Jones T, Smyth AM et al. DOCK8 is essential for T-cell survival and the maintenance of CD8 + T-cell memory. European Journal of Immunology. 2011 Dec;41(12):3423-3435. https://doi.org/10.1002/eji.201141759
Lambe, Teresa ; Crawford, Greg ; Johnson, Andy L. ; Crockford, Tanya L. ; Bouriez-Jones, Tiphaine ; Smyth, Aisling M. ; Pham, Trung H M ; Zhang, Qian ; Freeman, Alexandra F. ; Cyster, Jason G. ; Su, Helen C. ; Cornall, Richard J. / DOCK8 is essential for T-cell survival and the maintenance of CD8 + T-cell memory. In: European Journal of Immunology. 2011 ; Vol. 41, No. 12. pp. 3423-3435.
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