CHARACTERIZATION OF THE CHANGING LYMPHOCYTE POPULATIONS AND CYTOKINE EXPRESSION IN THE EXOCRINE TISSUES OF AUTOIMMUNE NOD MICE

NOD mice develop chronic lymphocytic invasion of the pancreas, submand ibular, and lacrimal glands leading to loss of insulin secretion, sali vary flow, and tear production. In this study, we have used flow cytom etric analyses and RT-PCR to track glandular lymphocyte populations an d cytokine expression spanning the initiation of autoimmune infiltrati on through the development of widespread autoimmune destruction of the salivary and lacrimal glands of NOD mice. Results demonstrate a predo minance of CD4(+) to CD8(+) lymphocytes and a similar predominance of T-cells versus B-cells in both the submandibular and lacrimal gland in filtrates. A temporal increase in memory (CD3(+)CD45RB(lo)) T-cells wa s also detected; however, naive (CD3(+)CD45RB(hi)) T-cell populations as well as a CD3(+), CD4(-)/CD8(-) double negative population were als o present. In addition, a skewing of the TCR V beta repertoire toward V beta 6(+) and V beta 8(+) lymphocytes was evident in both glandular infiltrates. Analyses of cytokine mRNA expression in the submandibular glands demonstrated an increase between 12 and 16 wk of age of severa l proinflammatory cytokines including IL-1 beta, IL-6, IL-7, IL-10, IF N gamma, TNF alpha, and inducible Nitric Oxide Synthase (iNOS). IL-4 s ynthesis was notably absent in both tissues. Cytokine mRNA transcripts detected in lacrimal tissue were similar to those seen in the submand ibular glands but appeared both earlier and more intensely. These find ings depict the progressive development of autoimmune exocrinopathy an d can be used as a foundation to explore the similarities and potentia l differences in the immunopathogenic lesions of several distinct tiss ues within the same host.