title: A canonical Vγ4Vδ4+ γδ T cell population with distinct stimulation requirements which promotes the Th17 response.
abstract: We previously reported a subset of γδ 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" Vγ4Vδ4+ 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 Vγ4Vδ4+ cells in the draining lymph nodes of DBA/1 and C57BL/6 mice and that the TCRs of the elicited Vγ4Vδ4+ 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 Vγ4Vδ4+ γδ 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 Vγ4Vδ4+ cells are recruited from Vγ4+ γδ 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 IFNγ, although αβ T cells need not be present. The CFA-elicited Vγ4Vδ4+ γδ T cells show a cytokine profile different from that of other previously described IL-17-producing γδ T cells. Finally, the Vγ4Vδ4+ subset appears to promote the Th17 αβ T cell response, suggesting its importance in mounting an effective immune response against certain pathogens.
authors.affiliation: Beacon Biotechnology, Aurora, CO 80045, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Roark
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.forename: Niyun
authors.initials: N
authors.lastname: Jin
authors.forename: M Kemal
authors.initials: MK
authors.lastname: Aydintug
authors.forename: Tamara
authors.initials: T
authors.lastname: Casper
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D005620:Freund's Adjuvant / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D020381:Interleukin-17 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; D005620:Freund's Adjuvant