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A canonical Vγ4Vδ4+ γδ T cell population with distinct stimulation requirements which promotes the Th17 response

  • Immunology in Colorado
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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.

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Acknowledgments

The authors thank Shirley Sobus and Josh Loomis for flow cytometry assistance, Philip Simonian (University of Colorado School of Medicine) for help with the Luminex cytokine assay and for scientific discussions, and Ross Kedl (National Jewish Health) for the B6.MyD88−/− mice. This work was supported by a research grant from the National Arthritis Research Foundation to CLR, and by NIH grants 2R01 AI 44920 and 1R56AI077594 to RLO, and by NIH grant 1R01 HL65410 to WKB.

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Authors and Affiliations

  1. Beacon Biotechnology, 12635 East Montview Blvd., Aurora, CO, 80045, USA

    Christina L. Roark

  2. Integrated Department of Immunology, National Jewish Health, 1400 Jackson St., Denver, CO, 80206, USA

    Yafei Huang, Niyun Jin, M. Kemal Aydintug, Tamara Casper, Willi K. Born & Rebecca L. O’Brien

  3. University of Colorado School of Medicine, 13001 E. 17th Place, Aurora, CO, 80045, USA

    Yafei Huang, Niyun Jin, M. Kemal Aydintug, Tamara Casper, Willi K. Born & Rebecca L. O’Brien

  4. Department of Ophthalmology, Doheny Eye Institute, University of Southern California, 1450 San Pablo St., Los Angeles, CA, 90033, USA

    Deming Sun

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  1. Christina L. Roark
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Correspondence to Rebecca L. O’Brien.

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Roark, C.L., Huang, Y., Jin, N. et al. A canonical Vγ4Vδ4+ γδ T cell population with distinct stimulation requirements which promotes the Th17 response. Immunol Res 55, 217–230 (2013). https://doi.org/10.1007/s12026-012-8364-9

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