Tfh Cell

T follicular helper (Tfh) cells are a specialized subset of CD4+ T-helper cells found in the follicles of tonsils, spleen, and thymus that assist in B-cell maturation. ICOS/ICOS-L interactions between activated T cell and DCs direct the differentiation of Tfh cells, and the transcription factor Bcl6 is essential for the differentiation.1,2 Unlike Th1 and Th2 cells, Bcl6 is preferentially expressed by Tfh cells. Tfh cells differ from Th1 and Th2 cells in terms of chemokine receptor expression, location and migration, function, cytokine production, and expression of transcription factors.1

During a germinal center (GC) reaction, Tfh cells perform their primary function by helping in the differentiation of B cells into effector cells and show increased levels of CD40L, ICOS, and IL-10.1 IL-21, produced by Tfh cells, potently stimulates the differentiation of immature B cells into plasma cells through IL-21R (which is predominant on B cells). Dysregulation and aberrant expression of Tfh cell-secreted molecules, including ICOS and IL-21, are important contributors to the development of autoimmune diseases and/or immunodeficiencies. Dysregulation of Tfh cells, resulting in the production of large amounts of IL-21 at nonlymphoid sites, may be associated with chronic T cell-mediated autoimmune inflammation.1

Tfh-cell differentiation and function are critically involved in regulating the immune response to pathogens, vaccines, autoimmune diseases, allergies, and organ transplant tolerance.2

​CD: cluster of differentiation; DC: dendritic cell; ICOS: inducible T-cell costimulator; ICOS-L: ICOS ligand; IL: interleukin; IL-21R: IL-21 receptor; Th1: type 1 T helper; Th2: type 2 T helper.


  • 1.

    King C, Tangye SG, Mackay CR. Annu Rev Immunol. 2008;26:741-766.​

  • 2.

    Crotty S. Immunity. 2019;50:1132-1148.​