title: Functional and molecular characterization of B cell-responsive V delta 1+ gamma delta T cells.
abstract: Cells expressing the V delta 1+ gene segment are a minor gamma delta T cell population in human peripheral blood but predominate in epithelial and (inflamed) tissues. The characteristic dendritic-like morphology of these gamma delta T cells is consistent with their putative immune surveillance role in epithelia. Their function, however, remains unknown. We and others previously reported that a subset of V delta 1+ gamma delta T cells proliferates after stimulation with Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCL), but not with fresh peripheral blood-derived B cells. These responses were independent of the type of T cell receptor (TcR) gamma chain co-expressed with the V delta 1 chain. The in vivo relevance of this LCL-mediated activation as well as the nature of the stimulatory ligand on the LCL is not well established. In this study, we tested the proliferative response of V delta 1+ LCL-responsive T cells against non-EBV-transformed B cells, activated through CD40 by murine EL4 B5 cells, and to a panel of B cell lines differing in the expression of EBV nuclear antigen proteins and adhesion/co-stimulatory molecules. The role of the Epstein-Barr virus-derived antigen in the induction of this response could be excluded as the activated (non-EBV-transformed) peripheral blood B cells were also able to induce a proliferative response in the LCL-responsive V delta 1+ T cells. Therefore, the stimulatory ligand on B cells is of cellular rather than of viral origin, and its expression is up-regulated upon activation of B cells. The expression of B7 and CD39 molecules on the surface of activated B cells appeared to be crucial since antibodies to these structures could block the induction of proliferation of the V delta 1+ T cells. Finally, we investigated the diversity of the responding V delta 1+ gamma delta T cell clones by sequence analysis of the TcR delta junctional regions. No restricted V-D-J sequences were found among the LCL-responsive V delta 1+ T cell clones, arguing strongly against a mono- or oligoclonal V delta 1+ gamma delta T cell response to LCL. These findings may explain the presence of polyclonally activated V delta 1+ T cells in inflamed tissues where activated B cells are often present.
authors.affiliation: Department of Immunohematology and Bloodbank, University Hospital Leiden, The Netherlands.
authors.forename: D L
authors.initials: DL
authors.lastname: Orsini
authors.forename: M
authors.initials: M
authors.lastname: van Gils
authors.forename: Y M
authors.initials: YM
authors.lastname: Kooy
authors.forename: L
authors.initials: L
authors.lastname: Struyk
authors.forename: G
authors.initials: G
authors.lastname: Klein
authors.forename: P
authors.initials: P
authors.lastname: van den Elsen
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D001081:Apyrase; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000502:physiology; D001483:Base Sequence; D002472:Cell Transformation, Viral; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D004854:Herpesvirus 4, Human; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D017931:DNA Primers; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen