title: IL-17A expression in HIV-specific CD8 T cells is regulated by IL-4/IL-13 following HIV-1 prime-boost immunization.
abstract: 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)Gag197-205-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)Gag197-205-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-13Rα2-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)Gag197-205-specific CD8 T cells were detected both in the lung and the spleen. However, at the transcriptional level, elevated TGF-β, IL-6, ROR-γt, 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-β, IL-6, ROR-γt, but not IL-23a, played a role in IL-17A regulation in K(d)Gag197-205-specific CD8 T cells. Collectively, our findings suggest that IL-4 and IL-13 differentially regulate the expression of IL-17A in K(d)Gag197-205-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.
authors.affiliation: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University , Canberra, Australia .
authors.forename: Jayashree
authors.initials: J
authors.lastname: Ravichandran
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: Shubhanshi
authors.initials: S
authors.lastname: Trivedi
authors.forename: Charani
authors.initials: C
authors.lastname: Ranasinghe
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018793:Interleukin-13; D020381:Interleukin-17; D010446:Peptide Fragments; D050800:STAT6 Transcription Factor; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus; D015847:Interleukin-4