IL-17A Expression in HIV-Specific CD8 T Cells Is Regulated by IL-4/IL-13 Following HIV-1 Prime-Boost Immunization

Although Th1 and Th2 cytokines can inhibit interleukin (IL)-17-secreting T cells, how these cells are regulated under different infectious conditions is still debated. Our previous studies have shown that vaccination of IL-4 and IL-13 gene knockout (KO) mice can induce high-avidity HIV K(d)Gag(197-205)-specific CD8 T cells with better protective efficacy. In this study, when IL-13, IL-4, STAT6 KO, and wild-type BALB/c mice were prime-boost immunized with an HIV poxviral modality, elevated numbers of IL-17A(+) splenic K(d)Gag(197-205)-specific CD8 T cells were observed in all the KO mice compared with the wt BALB/c control. Similarly, when wt BALB/c mice were immunized with IL-13R alpha 2-adjuvanted HIV vaccines (that transiently inhibited IL-13 activity and induced high-avidity CD8 T cells with enhanced protective efficacy), elevated IL-17A(+) K(d)Gag(197-205)-specific CD8 T cells were detected both in the lung and the spleen. However, at the transcriptional level, elevated TGF-beta, IL-6, ROR-gamma t, and IL-17A mRNA copy numbers were mainly detected in IL-4 KO, but not the IL-13 KO mice. These data suggested that TGF-beta, IL-6, ROR-gamma t, but not IL-23a, played a role in IL-17A regulation in K(d)Gag(197-205)-specific CD8 T cells. Collectively, our findings suggest that IL-4 and IL-13 differentially regulate the expression of IL-17A in K(d)Gag(197-205)-specific CD8 T cells at the transcriptional and translational level, respectively, implicating IL-17A as an indirect modulator of CD8 T cell avidity and protective immunity.