title: IL-21 regulates the differentiation of a human γδ T cell subset equipped with B cell helper activity.
abstract: Vγ9Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and display pleiotropic features. Here we report that coculture of Vγ9Vδ2 cells with phosphoantigen and IL-21 leads to selective expression of the transcription repressor Bcl-6 and polarization toward a lymphocyte subset displaying features of follicular B-helper T (T(FH)) cells. T(FH)-like Vγ9Vδ2 cells have a predominant central memory (CD27(+)CD45RA(-)) phenotype and express ICOS, CD40L and CXCR5. Upon antigen activation, they secrete IL-4, IL-10 and CXCL13, and provide B-cell help for antibody production in vitro. Our findings delineate a subset of human Vγ9Vδ2 lymphocytes, which, upon interaction with IL-21-producing CD4 T(FH) cells and B cells in secondary lymphoid organs, is implicated in the production of high affinity antibodies against microbial pathogens.
authors: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università degli Studi di Palermo, Palermo, Italy.
authors: Nadia
authors: N
authors: Caccamo
authors: Matilde
authors: M
authors: Todaro
authors: Marco P
authors: MP
authors: La Manna
authors: Guido
authors: G
authors: Sireci
authors: Giorgio
authors: G
authors: Stassi
authors: Francesco
authors: F
authors: Dieli
mesh_terms: D000915:Antibody Affinity / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007138:Immunoglobulin delta-Chains / Q000378:metabolism*; D007142:Immunoglobulin gamma-Chains / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology*; D051560:Proto-Oncogene Proteins c-bcl-6; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: C084103:BCL6 protein, human; D015704:CD4 Antigens; D018925:Chemokines; D004268:DNA-Binding Proteins; D007138:Immunoglobulin delta-Chains; D007142:Immunoglobulin gamma-Chains; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D000098546:Interleukin-21