Article: article from journal or magazin.
Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease.
Journal of Experimental Medicine
We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28-B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40-L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2-associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium.
Animals, Antigens, CD2/metabolism, Antigens, CD40/metabolism, Autoimmune Diseases/chemically induced, Autoimmune Diseases/immunology, Base Sequence, Blood Vessels/pathology, CD40 Ligand, Cytokines/biosynthesis, Cytotoxicity, Immunologic, Immune Complex Diseases, Membrane Glycoproteins/metabolism, Mercuric Chloride/pharmacology, Mice, Mice, Inbred Strains, Molecular Sequence Data, Signal Transduction, Skin/metabolism, Spleen/metabolism, T-Lymphocyte Subsets/immunology, Th2 Cells/immunology
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