A canonical V gamma 4V delta 4+gamma delta T cell population with distinct stimulation requirements which promotes the Th17 response

作者：Roark Christina L; Huang Yafei; Jin Niyun; Aydintug M Kemal; Casper Tamara; Sun Deming; Born Willi K; O'Brien Rebecca L^*

来源：Immunologic Research, 2013, 55(1-3): 217-230.

DOI：10.1007/s12026-012-8364-9

• Gamma/delta T cells
• Th17 response
• IL-17
• Dermis

We previously reported a subset of gamma delta T cells in mice which preferentially responds following intradermal immunization with collagen in complete Freund's adjuvant (CFA). These cells express a nearly invariant "canonical" V gamma 4V delta 4+ TCR. They are potent producers of IL-17A and promote the development of collagen-induced arthritis. In this study, we report that CFA emulsified with PBS alone (without collagen) is sufficient to induce a strong response of V gamma 4V delta 4+ cells in the draining lymph nodes of DBA/1 and C57BL/6 mice and that the TCRs of the elicited V gamma 4V delta 4+ cells in both strains heavily favor the canonical sequence. However, although both CFA and incomplete Freund's adjuvant (which lacks the killed mycobacteria present in CFA) induced V gamma 4V delta 4+ gamma delta T cell to expand, only CFA stimulated them to express IL-17A. The route of immunization was also critical, since intraperitoneal CFA induced only a weak response by these cells, whereas intradermal or subcutaneous CFA strongly stimulated them, suggesting that the canonical CFA-elicited V gamma 4V delta 4+ cells are recruited from V gamma 4+ gamma delta T cells normally found in the dermis. Their IL-17A response requires the toll-like receptor adapter protein MyD88, and their activation is enhanced by IFN gamma, although alpha beta T cells need not be present. The CFA-elicited V gamma 4V delta 4+ gamma delta T cells show a cytokine profile different from that of other previously described IL-17-producing gamma delta T cells. Finally, the V gamma 4V delta 4+ subset appears to promote the Th17 alpha beta T cell response, suggesting its importance in mounting an effective immune response against certain pathogens.

• 出版日期2013-3