title: Early preferential stimulation of gamma delta T cells by TNF-alpha.
abstract: Although recent findings indicate that gamma delta T cells influence both early innate and Ag-specific adaptive host responses, it has remained unclear what triggers gamma delta T cell reactivity. Investigating very early T cell activation in mouse and human models of bacterial infection, we measured CD69 expression as an indicator of early cellular activation. Both murine alpha beta and gamma delta T cells responded polyclonally to systemic bacterial infections, and to LPS. However, gamma delta T cells responded more strongly to the bacteria and to LPS. In vitro LPS-stimulated human T cells showed a similar differential response pattern. We identified TNF-alpha as mediator of the early differential T cell activation, and of differential proliferative responses. The stronger response of gamma delta T cells to TNF-alpha was correlated with higher inducible expression levels of TNF-Rp75. Among unstimulated splenocytes, more gamma delta T cells than alpha beta T cells expressed CD44 at high levels. The data suggest that TNF-Rp75 determines the differential T cell reactivity, and that most gamma delta T cells in the normal spleen are present in a presensitized state. As TNF-alpha stimulates activated T cells, it may early preferentially connect gamma delta T cell functions with those of cells that produce this cytokine, including activated innate effector cells and Ag-stimulated T lymphocytes.
authors.affiliation: National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lahn
authors.forename: H
authors.initials: H
authors.lastname: Kalataradi
authors.forename: P
authors.initials: P
authors.lastname: Mittelstadt
authors.forename: E
authors.initials: E
authors.lastname: Pflum
authors.forename: M
authors.initials: M
authors.lastname: Vollmer
authors.forename: C
authors.initials: C
authors.lastname: Cady
authors.forename: A
authors.initials: A
authors.lastname: Mukasa
authors.forename: A T
authors.initials: AT
authors.lastname: Vella
authors.forename: D
authors.initials: D
authors.lastname: Ikle
authors.forename: R
authors.initials: R
authors.lastname: Harbeck
authors.forename: R
authors.initials: R
authors.lastname: O'Brien
authors.forename: W
authors.initials: W
authors.lastname: Born
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002478:Cells, Cultured; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens