Transfer of Sjögren's syndrome‐like autoimmune lesions into SCID mice and prevention of lesions by anti‐CD4 and anti‐T cell receptor antibody treatment

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Abstract
We describe the successful transfer of murine Sjögren's syndrome-like autoimmune lesions from MRL/lpr mice (H-2k) to severe combined immunodeficiency (SCID) mice (H-2d) and prevention of lesions by anti-CD4 and -T cell receptor Vβ8 antibody treatment. Mononuclear cells (1 × 106) isolated from the inflammed submandibular salivary gland tissues of MRL/lpr mice were transferred intraperitoneally into SCID mice. Autoimmune lesions resembling those seen in Sjögren's syndrome developed in the salivary and lacrimal glands of SCID mice 8 weeks after the injection, whereas other organs did not show any lesion. This pathology resembles Sjögren's syndrome in humans involving both the salivary and lacrimal glands. Immunohistochemically, a major proportion of these infiltrating cells in transferred SCID mice were CD4+ and Vβ8+. When the spleen cells from MRL/lpr mice were injected, severe inflammatory lesions, probably resulting from a graft-versus host reaction, were observed in multiple organs of SCID mice. The disease could not be induced by intraperitoneal administration of the sera from MRL/lpr mice, or of the spleen cells from C3H/He (H-2k) and BALB/c (H-2d) mice. We detected autoantibody production specific for the salivary gland tissue in sera from transferred SCID mice. Moreover, we found that the lesions were prevented by administration of the isolated cells treated in vitro with anti-CD4 and anti-Vβ8 monoclonal antibodies. These results suggest that CD4- and Vβ8-bearing T cells are involved in recognizing an autopeptide and triggering autoimmunity in the salivary and lacrimal glands, and therapies designed with anti-CD4 and anti-Vβ8 antibodies may prove effective in treating the murine autoimmune disease.