Th17‐related cytokines contribute to recall‐like expansion/effector function of HMBPP‐specific Vγ2Vδ2 T cells after Mycobacterium tuberculosis infection or vaccination. Issue 2 (February 2015) - Shen, Hongbo
Abstract Whether cytokines can influence the adaptive immune response by antigen‐specific γδ T cells during infections or vaccinations remains unknown. We previously demonstrated that, during BCG/Mycobacterium tuberculosis (Mtb) infections, Th17‐related cytokines markedly upregulated when phosphoantigen‐specific Vγ2Vδ2 T cells expanded. In this study, we examined the involvement of Th17‐related cytokines in the recall‐like responses of Vγ2Vδ2 T cells following Mtb infection or vaccination against TB. Treatment with IL‐17A/IL‐17F or IL‐22 expanded phosphoantigen 4‐hydroxy‐3‐methyl‐but‐enyl pyrophosphate (HMBPP)‐stimulated Vγ2Vδ2 T cells from BCG‐vaccinated macaques but not from naïve animals, and IL‐23 induced greater expansion than the other Th17‐related cytokines. Consistently, Mtb infection of macaques also enhanced the ability of IL‐17/IL‐22 or IL‐23 to expand HMBPP‐stimulated Vγ2Vδ2 T cells. When evaluating IL‐23 signaling as a prototype, we found that HMBPP/IL‐23‐expanded Vγ2Vδ2 T cells from macaques infected with Mtb or vaccinated with BCG or Listeria ΔactA prfA*‐ESAT6/Ag85B produced IL‐17, IL‐22, IL‐2, and IFN‐γ. Interestingly, HMBPP/IL‐23‐induced production of IFN‐γ in turn facilitated IL‐23‐induced expansion of HMBPP‐activated Vγ2Vδ2 T cells. Furthermore, HMBPP/IL‐23‐induced proliferation of Vγ2Vδ2 T cells appeared to require APC contact and involve the conventional and novel protein kinase C signaling pathways. These findings suggest that Th17‐related cytokines can contribute to recall‐like expansion and effector function of Ag‐specific γδ T cells after infection or vaccination.