Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjögren's syndrome (SS) through up-regulated Th2 response.
Intraperitoneal administration with anti-CD86 (B7.2) MoAb into the murine model for primary SS in NFS/sld mutant mice resulted in dramatically inhibitory effects on the development of autoimmune lesions, while no significant effects were observed when the mice were administered with anti-CD80 (B7.1) MoAb. We found that spleen cells in the murine SS model treated with anti-CD86 MoAb showed a significant impairment of autoantigen-specific T cell proliferation. T cell activation markers (CD44high, CD45RBlow, Mel-14low) were significantly down-regulated in the spleen cells gated on CD4 in anti-CD86-treated mice. We detected a higher level of cytokine production of IL-4 from splenic T cells in anti-CD86-treated mice, but not of IL-2, and interferon-gamma (IFN-gamma), compared with those in the anti-CD80- and PBS-treated SS model. Moreover, serum autoantibody production against alpha-fodrin autoantigen was almost entirely suppressed in anti-CD86-treated mice. These data provide strong evidence that in autoimmune exocrinopathy resembling SS in NFS/sld mutant mice, the CD86 costimulatory molecule plays a crucial role in the initiation and subsequent progression of Th1-mediated autoimmunity in the salivary and lacrimal glands.
Saegusa
K
K
Department of Pathology, Tokushima University School of Dentistry, Tokushima, Japan.
Ishimaru
N
N
Yanagi
K
K
Haneji
N
N
Nishino
M
M
Azuma
M
M
Saito
I
I
Hayashi
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D051940:B7-2 Antigen; D002352:Carrier Proteins / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D013049:Spectrin
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D051940:B7-2 Antigen; D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D013049:Spectrin; C497965:Cd86 protein, mouse