title: TNF-alpha is a positive regulatory factor for human Vgamma2 Vdelta2 T cells.
abstract: Vgamma2 Vdelta2 T cells in human peripheral blood recognize phosphoantigen and play important roles in host defense and immunoregulation. The TCR is required for Vgamma2 Vdelta2 T cell responses to phosphoantigen, but less is known about soluble or cell-associated costimulatory molecules. In this study, we show that human Vgamma2 Vdelta2 T cell responses to phosphoantigen, including activation, proliferation, cytokine production, and tumor cell cytotoxicity, require TNF-alpha binding to its receptor, with a preference for TNFR2. Because stimulated Vgamma2 Vdelta2 cells also produce TNF-alpha, this may be a positive control mechanism to sustain the response. Impaired proliferation in the presence of TNF-alpha or TNFR blocking agents was partially rescued by a TLR2 agonist, Pam(3)Cys. Our studies demonstrate that TNF-alpha plays a critical role in regulating human Vgamma2 Vdelta2 T cell immune responses.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Haishan
authors.initials: H
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Luo
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha