DOCK2-deficiency causes defects in anti-viral T cell responses and poor control of herpes simplex virus infection
Randall, K. L.; Flesch, I. E. A.; Mei, Y.; Miosge, L. A.; Aye, R.; Aye, R.; Yu, Z.; Domaschenz, H.; Hollett, N.; Russell, T.; Stefanovic, T.; Wong, Y. C.; Goodnow, C. C.; Bertram, E.; Enders, A.; Tscharke, D.
Show abstract
The expanding number of rare immunodeficiency syndromes offers an opportunity to understand key genes that support immune defence against infectious diseases. However, patients with these diseases are by definition rare. In addition, any analysis is complicated by treatments and co-morbid infections requiring the use of mouse models for detailed investigations. Here we develop a mouse model of DOCK2 immunodeficiency and demonstrate that these mice have delayed clearance of herpes simplex virus type 1 (HSV-1) infections. Further, we found that they have a critical, cell intrinsic role of DOCK2 in the clonal expansion of anti-viral CD8+ T cells despite normal early activation of these cells. Finally, while the major deficiency is in clonal expansion, the ability of primed and expanded DOCK2-deficient CD8+ T cells to protect against HSV-1-infection is also compromised. These results provide a contributing cause for the frequent and devastating viral infections seen in DOCK2-deficient patients and improve our understanding of anti-viral CD8+ T cell immunity.
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