1. Treatment and prevention of experimental autoimmune neuritis with superagonistic CD28-specific monoclonal antibodies.
- Author
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Schmidt J, Elflein K, Stienekemeier M, Rodriguez-Palmero M, Schneider C, Toyka KV, Gold R, and Hünig T
- Subjects
- Adoptive Transfer, Animals, Cell Division immunology, Cell Line, Cell Movement immunology, Cells, Cultured, Female, Immunity, Active, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents therapeutic use, Injections, Intraperitoneal, Interferon-gamma biosynthesis, Lymphocyte Activation immunology, Myelin P2 Protein immunology, Neuritis, Autoimmune, Experimental pathology, Neuritis, Autoimmune, Experimental physiopathology, Peptide Fragments immunology, Rats, Rats, Inbred Lew, Sciatic Nerve immunology, Sciatic Nerve physiopathology, Severity of Illness Index, T-Lymphocytes immunology, T-Lymphocytes metabolism, T-Lymphocytes pathology, T-Lymphocytes transplantation, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal therapeutic use, CD28 Antigens immunology, Epitopes, T-Lymphocyte immunology, Neuritis, Autoimmune, Experimental immunology, Neuritis, Autoimmune, Experimental prevention & control
- Abstract
Two distinct CD28-specific mAb were used in treatment of active or adoptive transfer (AT)-experimental autoimmune neuritis (EAN): "superagonistic" JJ316 activates T cells without T cell receptor (TCR) occupancy, and conventional JJ319 activates T cells only in the presence of TCR-stimulation. Treatment with JJ316 during induction phase of active and adoptive-transfer experimental autoimmune encephalomyelitis (AT-EAN) dramatically reduced disease severity and improved nerve function as revealed by electrophysiology. JJ316 given 1 week before immunization had a preventive effect. By immunohistology, JJ316 markedly reduced TC infiltration of the sciatic nerve in active and AT-EAN. JJ319 was less effective. Ex vivo, JJ316 therapy reduced P2-specific proliferation and interferon-gamma (IFN-gamma) production of lymph node cells. We demonstrate preventive and therapeutic effects of a "superagonistic" mAb-mediated, TCR-independent CD28 stimulation in EAN, possibly with implications for therapy of autoimmune-inflammatory disorders.
- Published
- 2003
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