We sought to evaluate the antiviral immune response in patients with WASP deficiency in?vivo.
Viral clearance and associated immunopathology were measured after infection of WASP-deficient (WAS KO) mice with lymphocytic choriomeningitis virus (LCMV). Induction of antiviral CD8+ T-cell immunity and cytotoxicity was documented in WAS KO mice by means of temporal enumeration of total and antigen-specific T-cell numbers. Type I interferon (IFN-I) production was measured in serum in response to LCMV challenge and characterized in?vivo by using IFN-I reporter mice crossed with WAS KO mice.
WAS KO mice showed reduced viral clearance and enhanced immunopathology during LCMV infection. This was attributed to both an intrinsic CD8+ T-cell defect and defective priming of CD8+ T cells by dendritic cells (DCs). IFN-I production by WAS KO DCs was reduced both in?vivo and in?vitro.
These studies use a well-characterized model of persistence-prone viral infection to reveal a critical deficiency of CD8+ T-cell responses in murine WASP deficiency, in which abrogated production of IFN-I by DCs might play an important contributory role. These findings might help us to understand the immunodeficiency of WAS.