De novo donor-specific antibody (DSA) formation is a major problem in transplantation, and associated with long-term graft decline and loss as well as sensitization, limiting future transplant options. Forming high-affinity, long-lived antibody responses involves a process called the germinal center (GC) reaction, and requires interaction between several cell types, including GC B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. T follicular regulatory cells are an essential component of the GC reaction, limiting its size and reducing nonspecific or self-reactive responses.
An imbalance between helper function and regulatory function can lead to excessive antibody production. High proportions of Tfh cells have been associated with DSA formation in transplantation; therefore, Tfr cells are likely to play an important role in limiting DSA production. Understanding the signals that govern Tfr cell development and the balance between helper and regulatory function within the GC is key to understanding how these cells might be manipulated to reduce the risk of DSA development.
This review discusses the development and function of Tfr cells and their relevance to transplantation. In particular how current and future immunosuppressive strategies might allow us to skew the ratio between Tfr and Tfh cells to increase or decrease the risk of de novo DSA formation.
A comprehensive review by Wallin et al on T follicular regulatory T cell development, as well as their ability to control germinal center B cell responses and subsequent DSA production.
1 Transplant Research Immunology Group, Nuffield Department of Surgical Sciences, Level 6 John Radcliffe Hospital, Oxford.
Received 2 December 2017. Revision received 7 March 2018.
Accepted 9 March 2018.
E.F.W. was supported by a Kidney Research UK/MRC Clinical Fellowship.
The author declares no conflict of interest.
Correspondence: Elizabeth F. Wallin, Transplant Research Immunology Group, Nuffield Dept Surgical Sciences, Level 6 John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. (email@example.com).