Regulation of myelin basic protein-specific helper T cells in multiple sclerosis: generation of suppressor T cell lines.
Suppressor T cell (Ts) lines specific for myelin basic protein (MBP)-reactive helper T cell (Th) clones were generated from two patients with multiple sclerosis (MS) following a primary culture of peripheral blood mononuclear cells (PBMC) with MBP and cyclosporine A (CsA). These suppressor T cell lines were maintained in culture by alternate stimulation with MBP and antigen-presenting cells (APC). The Ts lines expressed preferentially the CD4 phenotype (5/6 Ts lines tested) and exhibited potent antigen-specific suppressor activity on the proliferation of MBP-specific Th clones and not on the T cell lines with other antigen specificity. For some Ts lines, a Ts-to-Th ratio of 1 was sufficient to inhibit the proliferation of MBP-specific T cells by 90%. The suppressor T cells obtained were weakly responsive to MBP and required the presence of the autologous PBMC for proliferation. Furthermore, proliferation of these suppressor T cell lines was restricted by HLA-DR molecules (for CD4+ Ts lines) and HLA class I (for a CD8+ Ts line). The suppressor T cell lines generated and the techniques described in this study may be helpful in our understanding of the events involved in the immune regulation in MS and other autoimmune diseases.
Department of Immunology, Dr. L. Willems Instituut, Diepenbeek, Belgium.
J W
JW
Zhang
M
M
Schreurs
R
R
Medaer
J C
JC
Raus
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D008222:Lymphokines; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine