T cell attractant chemokine expression initiates lacrimal gland destruction in nonobese diabetic mice

By inducing both adhesion and migration of lymphocytes, chemokines play an important role in immune and inflammatory responses. To learn how these pro cesses promote disease, we have examined the activities of chemokines in th e lacrimal glands (LG) of nonobese diabetic (NOD) mice, an animal model of Sjogren's syndrome (SS). The expression of three molecules in the chemokine superfamily, RANTES, IP-10 and lymphotactin, correlated with the local rec ruitment of lymphocytes into the LG of NOD mice. Both RANTES and IP-10 gene transcripts were first detected in these LG when the mice were 8 weeks of age and amounts increased markedly during the course of active disease; lym photactin mRNA was also expressed but at lower levels. In situ hybridizatio n of LG indicated that lymphocytic cells in the inflammatory infiltrates we re responsible for the production of RANTES and IP-10. Concomitant with the induction of chemokine expression was the appearance of cellular receptors for RANTES (CCR1, CCR5) and IP-10 (CXCR3). Furthermore, anti-RANTES treatm ent significantly reduced inflammation in the LG from NOD mice. In the SS-l ike disease of NOD mice, this distinct pattern of activity provides evidenc e for the contribution of these components to site- and time-specific recru itment of lymphocytes in the characteristic destruction of glandular struct ures.