The adaptor molecule MyD88 directly promotes CD8 T cell responses to vaccinia virus

Y Zhao, C De Trez, R Flynn, CF Ware… - The Journal of …, 2009 - journals.aai.org
Y Zhao, C De Trez, R Flynn, CF Ware, M Croft, S Salek-Ardakani
The Journal of immunology, 2009journals.aai.org
Vaccinia virus (VACV) elicits a robust CD8 T cell response that plays an important role in
host resistance. To date, there is little information on the molecules that are essential to
generate large pools of VACV-specific effector CD8 T cells. In this study, we show that the
adaptor molecule MyD88 is critical for the magnitude of primary CD8 T cell responses to
both dominant and subdominant VACV epitopes. MyD88−/− mice exhibit profound reduction
in CD8 T cell expansion and antiviral cytokine production. Surprisingly, the defect was not …
Abstract
Vaccinia virus (VACV) elicits a robust CD8 T cell response that plays an important role in host resistance. To date, there is little information on the molecules that are essential to generate large pools of VACV-specific effector CD8 T cells. In this study, we show that the adaptor molecule MyD88 is critical for the magnitude of primary CD8 T cell responses to both dominant and subdominant VACV epitopes. MyD88−/− mice exhibit profound reduction in CD8 T cell expansion and antiviral cytokine production. Surprisingly, the defect was not due to impaired APC function, as MyD88−/− dendritic cells matured normally and were able to promote strong CD8 T cell priming following VACV infection. Rather, adoptive transfer experiments demonstrated that intrinsic MyD88-dependent pathways in CD8 T cells were critical. MyD88-deficient CD8 T cells failed to accumulate in wild-type hosts and poor expansion of MyD88-deficient VACV-specific CD8 T cells resulted after virus infection. In contrast, no defect was evident in the absence of TRIF, TLR2, TLR4, TLR9, and IL-1R. Together, our results highlight an important role for MyD88 in initial antiviral CD8 T cell responses and suggest that targeting this pathway may be useful in promoting and sustaining anti-VACV immunity.
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