title: T Follicular Helper Cells in Transplantation.
abstract: 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.
authors.affiliation: 1 Department of Immunology and Infectious Disease, John Curtin School of Medical Research and Centre for Personalised Immunology, Australian National University, Canberra, Australia.2 Department of Renal Medicine, The Canberra Hospital, Canberra, Australia.3 Australian National University Medical School, Canberra, Australia.
authors.forename: Giles Desmond
authors.initials: GD
authors.lastname: Walters
authors.forename: Carola G
authors.initials: CG
authors.lastname: Vinuesa
mesh_terms: D064591:Allografts; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007378:Interleukins / Q000097:blood / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D016377:Organ Transplantation / Q000009:adverse effects; D010641:Phenotype; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D000098546:Interleukin-21
chemical_list: D007166:Immunosuppressive Agents; D007378:Interleukins; D007518:Isoantibodies; D000098546:Interleukin-21