Gammadelta receptor bearing T cells in scleroderma: enhanced interaction with vascular endothelial cells in vitro.
In view of the documented perivascular mononuclear cell infiltration in the involved organs in scleroderma (SSc) and the reported accumulation of gammadelta-T cells in SSc skin and lung, we evaluated gammadelta-T cell interaction with endothelial cells (EC) in vitro. gammadelta- and alphabeta-T cells were isolated from BPMN of SSc patients with early diffuse disease and of matched control subjects by an immunomagnetic method after stimulation with mycobacterium lysate and interleukin-2 for 2 weeks. Lymphocyte adhesion, proliferation, and cytotoxicity to EC were investigated. SSc gammadelta-T cells adhered to cultured EC and proliferated at higher rates than control cells. Furthermore, significant EC cytotoxicity by SSc gammadelta was seen. The cytotoxicity was blocked by addition of anti-gammadelta-TCR antibody and by anti-granzyme A antibody but not by anti-MHC class I and II antibodies. Expression of granzyme A mRNA was seen in five/five SSc gammadelta-T cells and in one/five control cells. alphabeta-T cells from both SSc and control subjects were significantly less interactive with EC than gammadelta-T cells. The data demonstrate EC recognition by SSc gammadelta-T cells and propose gammadelta-T cells as a possible effector cell type in the immune pathogenesis of SSc.
Kahaleh
M B
MB
Division of Rheumatology, Medical College of Ohio, Toledo, Ohio 43699, USA.
Fan
P S
PS
Otsuka
T
T
D002455:Cell Division; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology; D053804:Granzymes; D006801:Humans; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology; D012697:Serine Endopeptidases / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human