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

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69 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 - 1 Dec 2011

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Keywords

  • Human
  • Immunodeficiency
  • Memory
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lambe, T., Crawford, G., Johnson, A. L., Crockford, T. L., Bouriez-Jones, T., Smyth, A. M., Pham, T. H. M., Zhang, Q., Freeman, A. F., Cyster, J. G., Su, H. C., & 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