title: Notch signaling regulates follicular helper T cell differentiation.
abstract: Follicular helper T (TFH) cells are specialized in providing help for B cell differentiation and Ab secretion. Several positive and negative regulators of TFH cell differentiation have been described but their control is not fully understood. In this study, we show that Notch signaling in T cells is a major player in the development and function of TFH cells. T cell-specific gene ablation of Notch1 and Notch2 impaired differentiation of TFH cells in draining lymph nodes of mice immunized with T-dependent Ags or infected with parasites. Impaired TFH cell differentiation correlated with deficient germinal center development and the absence of high-affinity Abs. The impact of loss of Notch on TFH cell differentiation was largely independent of its effect on IL-4. These results show a previously unknown role for Notch in the regulation of TFH cell differentiation and function with implications for the control of this T cell population.
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Floriane
authors.initials: F
authors.lastname: Auderset
authors.forename: Steffen
authors.initials: S
authors.lastname: Schuster
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasnacht
authors.forename: Manuel
authors.initials: M
authors.lastname: Coutaz
authors.forename: Mélanie
authors.initials: M
authors.lastname: Charmoy
authors.forename: Ute
authors.initials: U
authors.lastname: Koch
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Favre
authors.forename: Anne
authors.initials: A
authors.lastname: Wilson
authors.forename: François
authors.initials: F
authors.lastname: Trottein
authors.forename: James
authors.initials: J
authors.lastname: Alexander
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Luther
authors.forename: H Robson
authors.initials: HR
authors.lastname: MacDonald
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
chemical_list: D051880:Receptors, Notch