IL-21 regulates the differentiation of a human γδ T cell subset equipped with B cell helper activity

• Published in: PloS one Vol. 7; no. 7; p. e41940
• Main Authors: Caccamo, Nadia, Todaro, Matilde, La Manna, Marco P, Sireci, Guido, Stassi, Giorgio, Dieli, Francesco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-07-2012; Public Library of Science (PLoS)
• Subjects: Antibodies; Antibody Affinity - drug effects; Antigen presentation; Antigens; B-Lymphocytes - immunology; Bcl-6 protein; Biology; CD27 antigen; CD4 antigen; CD4 Antigens - metabolism; CD40L protein; CD45RA antigen; Cell Differentiation - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemokines - biosynthesis; CXCL13 protein; CXCR5 protein; Cytokines; Dendritic cells; DNA-Binding Proteins - metabolism; E coli; Escherichia coli; Gene Expression Regulation - drug effects; Humans; Immunoglobulin delta-Chains - metabolism; Immunoglobulin gamma-Chains - metabolism; Immunoglobulins; Immunological memory; Immunotherapy; Interleukin 10; Interleukin 21; Interleukin 4; Interleukins - pharmacology; Lymphocytes; Lymphocytes B; Lymphocytes T; Major histocompatibility complex; Medicine; Microorganisms; Organs; Proto-Oncogene Proteins c-bcl-6; Studies; T cell receptors; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Transcription; Tuberculosis; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041940

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.