γδ T cells control humoral immune response by inducing T follicular helper cell differentiation

Rafael M. Rezende (), Amanda J. Lanser, Stephen Rubino, Chantal Kuhn, Nathaniel Skillin, Thais G. Moreira, Shirong Liu, Galina Gabriely, Bruna A. David, Gustavo B. Menezes and Howard L. Weiner
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Rafael M. Rezende: Harvard Medical School
Amanda J. Lanser: Harvard Medical School
Stephen Rubino: Harvard Medical School
Chantal Kuhn: Harvard Medical School
Nathaniel Skillin: Harvard Medical School
Thais G. Moreira: Harvard Medical School
Shirong Liu: Harvard Medical School
Galina Gabriely: Harvard Medical School
Bruna A. David: Federal University of Minas Gerais
Gustavo B. Menezes: Federal University of Minas Gerais
Howard L. Weiner: Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract γδ T cells have many known functions, including the regulation of antibody responses. However, how γδ T cells control humoral immunity remains elusive. Here we show that complete Freund’s adjuvant (CFA), but not alum, immunization induces a subpopulation of CXCR5-expressing γδ T cells in the draining lymph nodes. TCRγδ+CXCR5+ cells present antigens to, and induce CXCR5 on, CD4 T cells by releasing Wnt ligands to initiate the T follicular helper (Tfh) cell program. Accordingly, TCRδ−/− mice have impaired germinal center formation, inefficient Tfh cell differentiation, and reduced serum levels of chicken ovalbumin (OVA)-specific antibodies after CFA/OVA immunization. In a mouse model of lupus, TCRδ−/− mice develop milder glomerulonephritis, consistent with decreased serum levels of lupus-related autoantibodies, when compared with wild type mice. Thus, modulation of the γδ T cell-dependent humoral immune response may provide a novel therapy approach for the treatment of antibody-mediated autoimmunity.

Date: 2018
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DOI: 10.1038/s41467-018-05487-9

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