Follicular Regulatory T cells Positively Regulate Follicular Helper T Cells, Germinal Center B Cells and IgE Response in Peanut Allergic Mice

Abstract

Abstract Food allergy remains a major health problem in developed countries such as United States. However, the immunological mechanisms that control peanut allergy are largely unknown. In an oral sensitization food allergy model using peanut protein and cholera toxin (PCT), we found mice (Bcl6FC: FOXP3cre Bcl6 fl/fl) deficient in follicular T regulatory (Tfr) cells had lower follicular helper T (Tfh) cells and germinal center B (GCB) cells after two challenges. The decrease in Tfh/GCB cells was seen in both mesenteric Lymph Node and spleen responses. In this two-challenge model, peanut specific IgE, IgG1 and IgA antibody (Ab) responses were sharply decreased in Bcl6FC mice compared with wild type (WT) ones. However, after eight PCT challenges, Tfh and GCB cells were similar in Bcl6FC mice compared with WT, and peanut specific IgE was elevated in the absence of Tfr cells. We also show that Tfh/GCB cells are required for IgE production in this food allergy model. In mice with Blimp1-deficiency in T regulatory (Treg) cells (Blimp1FC: FOXP3cre Blimp1 fl/fl), Tfr, Tfh and GCB cells were significantly higher compared with WT or Bcl6FC mice while Treg derived IL-10 was much lower. Peanut specific Ab responses trended lower in Blimp1FC mice after two PCT challenges. Our data presented here is the novel evidence showing a positive regulation of Tfh/GCB cells and IgE response by Tfr cells, and suggest that a key regulatory pathway of Tfh/GCB cells and IgE response involves IL-10 production by Tfr cells. Supported by The AAI Careers in Immunology Fellowship Program.