title: T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells.
abstract: Effector T cell responses have long been viewed in the context of the Th1/Th2 paradigm. Recently, a third major subset of nonpolarized effector T cells that provides help to B cells has been identified. These T cells, termed T follicular helper (T(FH)) cells, home to the B cell areas of secondary lymphoid tissue, through interactions mediated via the chemokine receptor CXCR5 and its ligand CXCL13. Affymetrix microarrays were used to identify transcription factors, cytokines, and cell surface molecules that underlie the differentiation pathways and functional properties of the T(FH) subset. The transcriptional profile of human CXCR5(+) T(FH) cells was compared with that of Th1 and Th2 cells, which enabled the identification of numerous genes expressed preferentially by T(FH) cells, over the other effector subsets. Certain T(FH) genes were also expressed by B cells and thus appear to be particularly relevant for humoral immunity. Abs were used to confirm the expression of several factors. In particular, CD84 and CD200, the cytokine IL-21, and the transcription factor BCL6 were all strongly associated with T(FH) cells. Gene microarrays reveal a highly distinctive transcriptional profile for a third subset of effector T cells that differs markedly from Th1 and Th2 cells.
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chtanova
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.forename: Rebecca
authors.initials: R
authors.lastname: Newton
authors.forename: Nita
authors.initials: N
authors.lastname: Frank
authors.forename: Martin R
authors.initials: MR
authors.lastname: Hodge
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rolph
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D018959:CD57 Antigens / Q000032:analysis; D004268:DNA-Binding Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis; D000071176:Signaling Lymphocytic Activation Molecule Family; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D000098546:Interleukin-21
chemical_list: D015703:Antigens, CD; D018959:CD57 Antigens; C498970:CD84 protein, human; C095085:CXCR5 protein, human; D004268:DNA-Binding Proteins; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors; D000098546:Interleukin-21