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

  • Nat Commun. 2018 Aug 8;9(1):3151. doi: 10.1038/s41467-018-05487-9.
Rafael M Rezende  1 ,  Amanda J Lanser  2 ,  Stephen Rubino  2 ,  Chantal Kuhn  2 ,  Nathaniel Skillin  2 ,  Thais G Moreira  2 ,  Shirong Liu  2 ,  Galina Gabriely  2 ,  Bruna A David  3 ,  Gustavo B Menezes  3 ,  Howard L Weiner  2
Affiliations
  • 1. Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. [email protected].
  • 2. Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • 3. Center for Gastrointestinal Biology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
PMID: 30089795 DOI: 10.1038/s41467-018-05487-9
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.

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