UP-REGULATION OF CYTOKINE MESSENGER-RNA, ADHESION MOLECULE PROTEINS, AND MHC CLASS-II PROTEINS IN SALIVARY-GLANDS OF TGF-BETA-1 KNOCKOUT MICE - MHC CLASS-II IS A FACTOR IN THE PATHOGENESIS OF TGF-BETA-1 KNOCKOUT MICE

Mice homozygous for a disrupted TGF-beta 1 allele develop multiple lym phoproliferative disorders similar to those seen in the pseudolymphoma of Sjogren's syndrome. At 2 wk of age, these TGF-beta 1 mutant mice b egin to develop wasting syndrome and die at around 4 to 5 wk of age, W e studied salivary glands from symptomatic mutant mice >14 days of age , Reverse transcriptase-PCR analysis showed up-regulation of proinflam matory cytokine genes such as IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of int ercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion mol ecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining, To elucidate the role of MHC class II, salivary glands from TGF-beta 1/MHC class II double knoc kout mice were used to investigate the expression of adhesion molecule s and MHC class II, In spite of the existence of basal intercellular a dhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands, These results sug gest that MHC class II plays a significant role in the pathogenesis of TGF-beta 1 mutant mice, Although the mechanism that initiates multipl e inflammatory diseases in these mice remains unclear, the context rep orted here would provide insight into the immunopathology of Sjogren's syndrome.