The link between circulating follicular helper T cells and autoimmunity

Nat Rev Immunol. 2022 Sep;22(9):567-575. doi: 10.1038/s41577-022-00693-5. Epub 2022 Mar 11.

Abstract

Follicular helper T (TFH) cells provide help to B cells, supporting the formation of germinal centres that allow affinity maturation of antibody responses. Although usually located in secondary lymphoid organs, T cells bearing features of TFH cells can also be identified in human blood, and their frequency and phenotype are often altered in people with autoimmune diseases. In this Perspective article, I discuss the increase in circulating TFH cells seen in autoimmune settings and explore potential explanations for this phenomenon. I consider the multistep regulation of TFH cell differentiation by the CTLA4 and IL-2 pathways as well as by regulatory T cells and highlight that these same pathways are crucial for regulating autoimmune diseases. The propensity of infection to serve as a cue for TFH cell differentiation and a potential trigger for autoimmune disease development is also discussed. Overall, I postulate that alterations in pathways that regulate autoimmunity are coupled to alterations in TFH cell homeostasis, suggesting that this population may serve as a core sentinel of dysregulated immunity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Autoimmunity*
  • Cell Differentiation
  • Germinal Center
  • Humans
  • T Follicular Helper Cells
  • T-Lymphocytes, Helper-Inducer