Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjogren's syndrome (SS) through up-regulated Th2 response

Intraperitoneal administration with anti-CD86 (B7.2) MoAb into the murine m odel for primary SS in NFS/sld mutant mice resulted in dramatically inhibit ory 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 pr oliferation. T cell activation markers (CD44(high), CD45RB(low), Mel-14(low )) were significantly down-regulated in the spleen cells gated on CD4 in an ti-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 i nterferon-gamma (IFN-gamma), compared with those in the anti-CD80- and PBS- treated SS model. Moreover, serum autoantibody production against alpha-fod rin autoantigen was almost entirely suppressed in anti-CD86-treated mice. T hese data provide strong evidence that in autoimmune exocrinopathy resembli ng SS in NFS/sld mutant mice, the CD86 costimulatory molecule plays a cruci al role in the initiation and subsequent progression of Th1-mediated autoim munity in the salivary and lacrimal glands.