Cognate T and B cell interaction and association of follicular helper T cells with B cell responses in Vibrio cholerae O1 infected Bangladeshi adults

Abstract

Vibrio cholerae O1 can cause life threatening diarrheal disease if left untreated. T cells can play critical roles in inducing B cell mediated immunity. As the mechanism of T cell dependent B cell maturation is not well established, we hypothesized that a specific population of T (follicular helper T, Tfh)) cells, are involved in B cell maturation following cholera. We found flowcytometrically that V. cholerae infection induces significant increases in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize cholera toxin most prominently, with lessened responses to V. cholerae membrane preparation (MP) and Vibrio cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after cholera can stimulate class switching of co-cultured, isolated B cells from patients with cholera, leading to production of the more durable IgG antibody isotype colorimetrically. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during cholera directly in gut mucosa of biopsied samples, at the single cell level if feasible.

Posttranslational Regulation of IL-23 Production Distinguishes the Innate Immune Responses to Live Toxigenic versus Heat-Inactivated Vibrio cholerae

“…IL-23 is a member of a group of cytokines that stimulate naive T cells to differentiate into Th17 cells, and among this group of cytokines, IL-23 is known to further differentiate Th17 cells into T follicular helper (Tfh) cells (30). Antigen-specific Tfh cells are thought to be critical for the development of protective memory B cell responses that mediate long-term immunity, and a recent study found that circulating Tfh cells in patients with cholera affect subsequent antigen-specific B cell development and consequent immunoglobulin production (31). IL-23 stimulates Th17 cells, and we previously observed that Th17-associated cytokines are activated in cholera patients to a greater degree than in OCV recipients (3).…”

Update on Environmental and Host Factors Impacting the Risk of Vibrio cholerae Infection

“…After V. cholerae infection, the early induction of V. cholerae -specific T follicular helper cells (Tfh) has been correlated with later memory B cell responses to the same V. cholerae antigens. In vitro, Tfh cells isolated from cholera patients induced class-switching in a B cell–Tfh coculture . Overall, it seems that T cell-mediated V. cholerae responses may contribute to V. cholerae protective immunity, potentially through T cell help or other mechanisms that are not yet understood …”

“…In vitro, Tfh cells isolated from cholera patients induced class-switching in a B cell–Tfh coculture . Overall, it seems that T cell-mediated V. cholerae responses may contribute to V. cholerae protective immunity, potentially through T cell help or other mechanisms that are not yet understood …”

“…In vitro, Tfh cells isolated from cholera patients induced class-switching in a B cell−Tfh coculture. 53 Overall, it seems that T cell-mediated V. cholerae responses may contribute to V. cholerae protective immunity, potentially through T cell help or other mechanisms that are not yet understood. 53 ■ HOST RISK FACTORS Age, nutritional, and genetic factors are known to impact susceptibility to V. cholerae infection; a summary of characteristics that may contribute to susceptibility is shown in Figure 2.…”

Bacteria That Cause Enteric Diseases Stimulate Distinct Humoral Immune Responses

“…V. cholerae infection also induces the development of circulating Tfh cells. These Tfh cells provide help to activated B cell leading to secretion class-switched antibodies by plasma cells and development of antigen-specific memory B cells ( 66 ).…”