Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease.
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.
Biancone
L
L
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129, USA.
Andres
G
G
Ahn
H
H
Lim
A
A
Dai
C
C
Noelle
R
R
Yagita
H
H
De Martino
C
C
Stamenkovic
I
I
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D001483:Base Sequence; D001808:Blood Vessels / Q000473:pathology; D018801:CD2 Antigens / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D007105:Immune Complex Diseases; D008562:Membrane Glycoproteins / Q000378:metabolism; D008627:Mercuric Chloride / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D018801:CD2 Antigens; D019013:CD40 Antigens; D016207:Cytokines; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D008627:Mercuric Chloride