Chronic Heat Stress Inhibits Immune Responses to H5N1 Vaccination through Regulating CD4(+)CD25(+)Foxp3(+) Tregs

Chronic heat stress (CHS) is known to have negative impacts on the immune responses in animals and increases their susceptibility to infections including the highly pathogenic avian influenza virus H5N1. However, the role of regulatory T cells (Tregs) in CHS immunosuppression remains largely undefined. In this study, we demonstrated a novel mechanism by which CHS suppressed both Th1 and Th2 immune responses and dramatically decreased the protective efficacy of the formalin-inactivated H5N1 vaccine against H5N1 influenza virus infection. This suppression was found to be associated with the induced generation of CD4(+)CD25(+)FoxP3(+) Tregs and the increased secretions of IL-10 and TGF-β in CD4(+) T cells. Adoptive transfer of the induced Tregs also suppressed the protective efficacy of formalin-inactivated H5N1 virus immunization. Collectively, this study identifies a novel mechanism of CHS immunosuppression mediated by regulating CD4(+)CD25(+)Foxp3(+) Tregs.