Induction of resistance to active experimental allergic encephalomyelitis by myelin basic protein-specific Th2 cell lines generated in the presence of glucocorticoids and IL-4.
We have produced T cell lines with a Th2 phenotype in the presence of IL-4 and the glucocorticoid dexamethasone (DEX). IL-4 and DEX together were more effective in inducing a Th2 response than IL-4 alone. Myelin basic protein (MBP)-specific Th2 lines were obtained and their ability to induce experimental allergic encephalomyelitis (EAE) was studied. Lines treated with IL-4 and DEX did not transfer passive EAE and did not induce cellular infiltration into the central nervous system as opposed to the encephalitogenic Th1 lines. Lines treated with IL-4 and DEX did not protect animals from the effect of encephalitogenic Th1 lines when the two were injected together. However, a high proportion of animals injected with IL-4 + DEX-treated lines became refractory to the development of EAE after immunization with MBP; that is, it was possible to induce resistance to active EAE without prior episodes of disease. Interestingly, animals injected with T cell lines had accelerated antibody responses against MBP and the predominant isotype was dependent on the cytokines synthesized by the T cell line injected. There was not evidence that the resistance to active EAE was due to anergy of MBP-reactive cells or the action of CD8+ cells. Our data suggest that MBP-specific T cell lines prevent the induction of disease by deviating the reactivity to MBP from a cell-mediated to a humoral one and not merely from a Th1 to a Th2 response.
Ramírez
F
F
Medical Research Council, Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, GB. framirez@molbiol.ox.ac.ul
Mason
D
D
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology*; D015213:Neuroimmunomodulation; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D001323:Autoantibodies; D005938:Glucocorticoids; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma