TRANSFER OF SJOGRENS SYNDROME-LIKE AUTOIMMUNE LESIONS INTO SCID MICE AND PREVENTION OF LESIONS BY ANTI-CD4 AND ANTI-T CELL-RECEPTOR ANTIBODY TREATMENT

We describe the successful transfer of murine Sjogren's syndrome-like autoimmune lesions from MRL/lpr mice (H-2(k)) to severe combined immun odeficiency (SCID) mice (H-2(d)) and prevention of lesions by anti-CD4 and -T cell receptor V beta 8 antibody treatment. Mononuclear cells ( 1 x 10(6)) isolated from the inflammed submandibular salivary gland ti ssues of MRL/lpr mice were transferred intraperitoneally into SCID mic e. Autoimmune lesions resembling those seen in Sjogren's syndrome deve loped in the salivary and lacrimal glands of SCID mice 8 weeks after t he injection, whereas other organs did not show any lesion. This patho logy resembles Sjogren's syndrome in humans involving both the salivar y and lacrimal glands. Immunohistochemically, a major proportion of th ese infiltrating cells in transferred SCID mice were CD4(+) and V beta 8(+). When the spleen cells from MRL/lpr mice were injected, severe i nflammatory lesions, probably resulting from a graft-versus host react ion, 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-2(k)) and BALB/c (H-2( d)) mice. We detected autoantibody production specific for the salivar y gland tissue in sera from transferred SCID mice. Moreover, we found that the lesions were prevented by administration of the isolated cell s treated in vitro with anti-CD4 and anti-V beta 8 monoclonal antibodi es. These results suggest that CD4- and V beta 8-bearing T cells are i nvolved in recognizing an autopeptide and triggering autoimmunity in t he salivary and lacrimal glands, and therapies designed with anti-CD4 and anti-V beta 8 antibodies may prove effective in treating the murin e autoimmune disease.