title: The development and fate of follicular helper T cells defined by an  IL-21 reporter mouse.
abstract: Germinal centers require CD4⁺ follicular helper T cells (TFH cells), whose hallmark is expression of the transcriptional repressor Bcl-6, the chemokine receptor CXCR5 and interleukin 21 (IL-21). To track the development and fate of TFH cells, we generated an IL-21 reporter mouse by introducing sequence encoding green fluorescent protein (GFP) into the Il21 locus; these mice had expression of IL-21–GFP in CD4⁺CXCR5⁺PD-1⁺ TFH cells. IL-21–GFP⁺ TFH cells were multifunctional helper cells that coexpressed several cytokines, including interferon-g (IFN-g), IL-2 and IL-4. TFH cells proliferated and gave rise to transferrable memory cells with plasticity, which differentiated after recall into conventional effector helper T cells and TFH cells. Thus, we demonstrated that TFH cells were not terminally differentiated but instead retained the flexibility to be recruited into other helper T cell subsets and nonlymphoid tissues.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Katja
authors.initials: K
authors.lastname: Lüthje
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimohakamada
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Amanda
authors.initials: A
authors.lastname: Light
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D000943:Antigens, Differentiation; C513179:CXCR5 protein, mouse; D016207:Cytokines; C556062:IL10 protein, mouse; D007376:Interleukin-2; D007378:Interleukins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D000098546:Interleukin-21