Session Speaker

A Distinct Role of CD4⁺ Th17 and Th17-Stimulated CD8⁺CTL in Induction of Experimental Autoimmune Encephalomyelitis and Antitumor Immunity
Manjunatha Ankathatti Munegowda and Jim Xiang
Canada

CD4⁺ Th17 and CD8⁺ T cells can induce experimental autoimmune encephalomyelitis (EAE) and eradicate established tumors. To assess their potential relationship, we generated RORγt-expressing and IL-17-secreting ovalbumin (OVA)- or myelin oligodendrocyte glycoprotein (MOG)-specific CD4⁺ Th17 cells by cultivation of OVA-pulsed dendritic cells (DC_OVA) with CD4⁺ T cells derived from T cell receptor transgenic OTII mice or MOG_35-55 peptide-pulsed splenocytes with CD4⁺ T cells purified from MOG_35-55 immunization-induced EAE C57BL/6 mice in presence of IL-6/IL-23/TGF-β (each, 10 ng/ml). We found that OVA-specific CD4⁺ Th17 cells which acquire MHC/peptide (pMHC) I and costimulatory molecules by DC_OVA activation stimulate OVA-specific CD8⁺ cytotoxic T lymphocyte (CTL) responses and antitumor immunity. The stimulatory effect is mediated by acquired CD80 costimulation and targeted to CD8⁺ T cells in vivo via acquired pMHC I complexes. CD4⁺ Th17-stimulated CD8⁺ CTL, but not Th17 cells with no direct in vitro killing activity play a major therapeutic role in eradication of established OVA-expressing tumors. We also found that MOG-specific CD4⁺ Th17 cells stimulate MOG-specific CD8⁺ CTL responses, and both CD4⁺ Th17 and Th17-stimulated CD8⁺ CTL are involved in induction of EAE with a major pathogenic role played by the former. Taken together, our data elucidate a distinct role of CD4⁺ Th17 and Th17-stimulated CD8⁺ CTL in induction of EAE and antitumor immunity.