The darker side of follicular helper T cells: from autoimmunity to immunodeficiency.

Follicular helper T (T(FH)) cells represent a distinct subset of CD4⁺ helper T (T(H)) cells specialized in providing help to B cells. They are characterized by their unique transcriptional profile (Bcl6), surface marker expression (CXCR5, PD-1, ICOS and CD40L) and cytokine production pattern (IL-21 and IL-6). T(FH) cells provide help to B cells both to form germinal centers (GCs) and to differentiate into memory B cells and plasma cells for generation of humoral responses. However, there is emerging evidence that implicates T(FH) cells in the development of various human pathologies, such as autoimmune diseases, immunodeficiency and lymphoma. This review focuses on the current progress in this area including mouse and human studies. A clearer understanding of the mechanisms of T(FH) cell-mediated immunity and pathology may be exploited for rational development of therapeutic strategies.