PREVENTION OF ADOPTIVE TRANSFER OF MURINE SJOGRENS-SYNDROME INTO SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE BY ANTIBODIES AGAINST INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1)

We have analysed the role of ICAM-1 and LFA-1 during development of au toimmune sialadenitis in MRL/lpr mice by direct analysis of RNA obtain ed from the salivary gland tissues, and the therapeutic effects with a ntibody administration on adoptive transfer system into SCID mice. The expression of cell adhesion molecules was assessed by using reverse t ranscriptase polymerase chain reaction (RT-PCR) and Southern blot anal ysis, and immunohistochemical analysis. Up-regulated expression of ICA M-1 mRNA was observed before the onset of inflammatory lesions in the salivary glands at 1 month and 2 months old, and thereafter LFA-1 mRNA was expressed within the typical inflammatory lesions, resembling hum an Sjogren's syndrome in MRL/lpr mice. Immunohistochemically, ICAM-1 w as localized exclusively in the endothelial cells of varying sized blo od vessels before the onset of disease, and LFA-1 expressing inflammat ory cells were found within these lesions. When the therapeutic effect s in vivo were examined, antibodies to ICAM-1 in combination with anti -LFA-1 prevented adoptive transfer of Sjogren's syndrome in MRL/lpr mi ce into SCID mice, while no significant effect was found when treated with either antibody. These findings indicate that in Sjojgren's syndr ome-like autoimmune lesions in MRL/lpr mice the ICAM-1/LFA-1 pathway m ay play a crucial role in the initiation and subsequent progression of T cell-mediated autoimmunity in the salivary and lacrimal glands of M RL/lpr mice.