Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 2, Pages 442-451Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201444635
Keywords
gamma delta T cells; IL-17/IL-22; IL-23; Phosphoantigen; Tuberculosis
Categories
Funding
- National Program Project grant [ZX10003]
- National Institutes of Health [OD015092, RR13601, HL64560, AI106590]
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Whether cytokines can influence the adaptive immune response by antigen-specific gamma delta 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 V gamma 2V delta 2 T cells expanded. In this study, we examined the involvement of Th17-related cytokines in the recall-like responses of V gamma 2V delta 2 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 V gamma 2V delta 2 T cells from BCG-vaccinated macaques but not from naive 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 V gamma 2V delta 2 T cells. When evaluating IL-23 signaling as a prototype, we found that HMBPP/IL-23-expanded V gamma 2V delta 2 T cells from macaques infected with Mtb or vaccinated with BCG or Listeria-actA prfA*-ESAT6/Ag85B produced IL-17, IL-22, IL-2, and IFN-gamma. Interestingly, HMBPP/IL-23-induced production of IFN-gamma in turn facilitated IL-23-induced expansion of HMBPP-activated V gamma 2V delta 2 T cells. Furthermore, HMBPP/IL-23-induced proliferation of V gamma 2V delta 2 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 gamma delta T cells after infection or vaccination.
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