title: Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression.
abstract: The generation of high-affinity antibody-secreting plasma cells critically depends on the presence of CD4 T cells during the germinal center (GC) reaction. GC T cells are so far incompletely characterized in terms of phenotype and function. Here, we show that human follicular B helper T (T(FH)) cells are characterized by high expression of the homeostatic chemokine receptor CXCR5 and the costimulatory molecule ICOS, but not CD57 expression. CXCR5(hi)ICOS(hi) CD4 T cells are the most potent inducers of IgG production that also secrete large amounts of the B cell-attracting chemokine CXCL13. CXCR5(hi)ICOS(hi) CD4 T cells differ from other tonsillar CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large-scale gene expression analysis revealed that T(FH) cells are only distantly related to CXCR5(-) and CXCR5(+) central memory T (T(CM)) as well as effector memory T (T(EM)) cells present in the periphery. CXCR5(hi)ICOS(hi) CD4 T cells appear to be terminally differentiated T helper cells that express a unique set of transcription factors related to the Notch signaling pathway and thus differentiate independent of other T helper cell populations.
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: Ata-Ur
authors.initials: AU
authors.lastname: Rasheed
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Rahn
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Gerd
authors.initials: G
authors.lastname: Müller
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018959:CD57 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D008211:Lymphocyte Cooperation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018959:CD57 Antigens; C095085:CXCR5 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine