Lymphocyte-fibroblast adhesion induced by interferon-gamma.
Adhesion of lymphocytes to vascular endothelium is thought to be of importance in regulating the passage of lymphocytes from the circulation to areas of inflammation. Evidence suggests the presence of site-specific lymphocyte receptor molecules on the endothelial cell surface which can be modulated by soluble immune factors. The factors responsible for maintaining lymphocyte infiltration at tissue sites are unknown. We have examined the adherence of human peripheral blood T lymphocytes to human fibroblast monolayers in vitro and the role of interferon-gamma in enhancing adherence. Treatment of fibroblasts with interferon-gamma resulted in an increase in the number of adherent T cells in a dose- and time-dependent manner. Enhanced adhesion was noted as early as 4 hr after interferon stimulation (291 +/- 7 T cells/field vs 51 +/- 10 without IFN stimulation) and binding was further increased by lengthening the exposure time of fibroblasts to interferon up to 72 hr (475 +/- 86 T cells/field). Kinetic and inhibition experiments using monoclonal antibody to HLA-DR demonstrated that adhesion of T lymphocytes to interferon-stimulated fibroblasts proceeds by a mechanism independent of DR induction. In addition, adherence was not histocompatibility antigen-restricted, as adherence to autologous and allogeneic fibroblast monolayers was not significantly different. Nonadherent T cells, collected at the end of adhesion assays, were deficient in their capacity to bind to a second interferon-treated monolayer, suggesting the depletion of a subpopulation of T cells responsible for adhesion. Alterations of fibroblasts in vivo by immune cell-derived cytokines may be an important mechanism for the localization of lymphocytes at sites of connective tissue inflammation.
D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology*; D006681:HLA-D Antigens / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D009005:Monosaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology*
D006681:HLA-D Antigens; D009005:Monosaccharides; D007371:Interferon-gamma