Interactions between lymphocytes and dermal fibroblasts: an in vitro model of cutaneous lymphocyte trafficking.
Cultures of dermal fibroblasts were established from skin biopsies of CBA mice and used to study the interactions with murine T-lymphocytes. Electron microscopy showed that zones of contact developed between the fibroblasts and the T-cells, particularly after mitogenic activation. The adhesion of the lymphocytes was temperature-dependent, and many more lymphoblasts than resting cells attached to the fibroblast monolayers. Flow cytometry analysis of the adherent population showed that the most prominent type of resting lymphocyte was of the CD4 phenotype, which was also observed using a T-helper lymphoid cell line. However, neither the CD4 nor the CD8 (T-cytotoxic) antigens were involved in the binding process, and while the fibroblasts expressed Class I MHC molecules (but not Class II), these also had no role in mediating lymphocyte adhesion. Although the fibroblasts did not express the ligand Mala-2, the murine homologue of human ICAM-1, a monoclonal antibody against LFA-1, its cognate receptor on the lymphocytes, nevertheless effectively inhibited binding. T-cell attachment was also partially prevented by antibody against the lymphocyte CD2 antigen and by RGDS, a protein epitope known to mediate a number of receptor-integrin interactions. Moreover, this peptide also rapidly and preferentially detached T-lymphocytes which had previously adhered to the fibroblast monolayers. Lymphocyte binding was substantially elevated following treatment of the fibroblasts with cytokines such as tumor necrosis factor-alpha and interferon-gamma, but not interleukin-1 alpha. This increase in adhesiveness was, however, almost completely abolished by monoclonal antibodies specific for LFA-1 or for Mala-2. The results of this study show that while lymphocytes recognize fibroblasts normally via a number of constitutively expressed receptor-integrin interactions, their adhesion can also be modulated by cytokine-induced changes in the expression of other surface ligands.
Cell Enzymology Unit, Kennedy Institute of Rheumatology, London, United Kingdom.
D
D
Abraham
S
S
Bokth
G
G
Bou-Gharios
J
J
Beauchamp
I
I
Olsen
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007372:Interferons / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D012867:Skin / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000954:Antigens, Surface; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons