Role of T follicular helper and T follicular regulatory cells in antibody-mediated rejection: new therapeutic targets?

Abstract

Purpose of reviewAntibody-mediated rejection (AbMR) after solid organ transplantation is tightly controlled by multiple cells of the immune system. Tfh and Tfr cells are essential controllers of antibody responses making them putative targets for therapeutics. However, the mechanisms of how Tfh and Tfr cells regulate B cell and antibody responses are not completely understood. Here, we summarize recent studies elucidating the functions of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells as well as their possible roles in regulating AbMR in solid organ transplantation. Recent findingsNew tools have been developed to study the roles of Tfh and Tfr cells in specific disease states, including AbMR after solid organ transplantation. These tools suggest complex roles for Tfh and Tfr cells in controlling antibody responses. Nevertheless, studies in solid organ transplant rejection suggest that Tfh and Tfr cells may be high value targets for therapeutics. However, specific strategies to target these cells are still being investigated. SummaryAbMR is still a substantial clinical problem that restricts long-term survival after solid organ transplantation. Growing evidence has demonstrated a pivotal role for Tfh and Tfr cells in controlling AbMR. In addition to providing an early indication of rejection as a biomarker, targeting Tfh and Tfr cells as a therapeutic strategy offers new hope for alleviating AbMR.

IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

“…Although Tfh cells have been implicated in controlling rejection after transplantation, the origins and precise functions of these cells in allogeneic B cell responses and rejection pathology are relatively unknown. A current paradigm suggests that Tfh cells are a uniform population; however, newer data suggest that Tfh cells can exist as unique subsets with distinct roles in disease progression ( 13 ). In some cases, these Tfh subsets have been denoted by their cytokine production.…”

Editorial: Mechanistic and therapeutic advances in antibody-mediated rejection: reasons to be optimistic

“…Although most research in the field of alloantibody formation focused on B cells, T follicular and regulatory cells (Tfh and Tfr, respectively) represent key cell populations for germinal center B cell maturation leading to the formation of highly functional antibodies. In their review, Zhang and Sage [6] outline the critical role of Tfh and Tfr cells in modulating DSA formation and ABMR in both preclinical models and in humans. These cells could be used as a biomarker of DSA formation and/or as a therapeutic target to prevent DSA formation and, potentially, an ongoing chronic AMR.…”