A distinct role of CD4+ Th17 and Th17-stimulated CD8+ CTL in induction of antitumor immunity and experimental autoimmune encephalomyelitis (101.5)

Abstract

Abstract Th17 and CD8+ cytotoxic T lymphocytes(CTL) cells eradicate established tumors and induce experimental autoimmune encephalomyelitis(EAE). To assess their potential relationship, we generated ovalbumin(OVA) or myelin oligodendrocyte glycoprotein(MOG) specific Th17 cells by in vitro cultivation of OVA-pulsed dendritic cells(DCova) with CD4 T cells derived from T cell receptor transgenic OTII mice or MOG peptide-pulsed splenocytes with CD4 T cells purified from MOG immunization induced EAE C57BL/6 mice. We found these Th17 cells expressed transcriptional factor RORγt and secreted IL17. We also found that OVA-specific Th17 cells which acquired major histocompatibility complex/peptide(pMHC) I and costimulatory molecules by DCova activation stimulated OVA-specific CTL response and antitumor immunity against OVA-expressing BL6-10ova tumor. The stimulatory effect is mediated by acquired CD80 costimulation and targeted to CD8 T cells in vivo via acquired pMHC I complexes. Th17-stimulated CTL, but not the Th17 cells shown to have no in vitro killing activity play a major therapeutic role in eradication of early stage of BL6-10ova tumors(3mm dia). We also found that MOG-specific Th17 cells stimulated MOG-specific CTL responses, and both Th17 cells and Th17-stimulated CTL are involved in induction of EAE with a major pathogenic role played by the former. In total our data elucidate a distinct role of Th17 cells and Th17-stimulated CTL in induction of antitumor immunity and EAE.