T Follicular Helper Cells in Transplantation

Transplantation. 2016 Aug;100(8):1650-5. doi: 10.1097/TP.0000000000001217.


The recently described T follicular helper (Tfh) cell is required for the production of high affinity antibody. After contact with follicular dendritic cells, Tfh cells move into the germinal centre and provide help to B cells both by direct B cell-T cell interaction and production of IL-21. This drives proliferation, differentiation, and affinity maturation of the B cells to produce plasma cells capable of secreting high-affinity antibody. Circulating Tfh cells are produced by movement of Tfh cells from lymph nodes after dendritic cell contact. A reduction of Tfh cell-associated molecules is linked with increased expression of other chemokine receptors to form Th1-, Th2-, and Th17-like Tfh cells. These circulating Tfh cells are able to help B cells in vitro and to move into target tissues to support antibody production. Alloantibody production is dependent on T-cell help via the indirect pathway. Antibody-mediated rejection is therefore dependent on Tfh cells. Animal data suggest that Tfh cells and B cells migrate to the allograft and are involved in alloantibody production within a tertiary lymphoid organ. There is some data supporting the same process within human allografts. The requirement for T-cell help provides a potential therapeutic target in the treatment of antibody-mediated rejection.

Publication types

  • Review

MeSH terms

  • Allografts
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Chemotaxis, Leukocyte
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Graft Rejection / blood
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Humans
  • Immunity, Humoral* / drug effects
  • Immunosuppressive Agents / therapeutic use
  • Interleukins / blood
  • Interleukins / immunology
  • Isoantibodies / blood
  • Isoantibodies / immunology
  • Lymphocyte Activation* / drug effects
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Organ Transplantation* / adverse effects
  • Phenotype
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Treatment Outcome


  • Immunosuppressive Agents
  • Interleukins
  • Isoantibodies
  • interleukin-21