ANALYSIS OF LEUKOCYTES RECRUITED TO THE PANCREAS BY DIABETOGENIC T-CELL CLONES

To investigate host leukocytes recruited to the pancreas by diabetogen ic T cells, we administered islet-specific CD4(+) T cell clones to 2-w eek-old nonobese diabetic (NOD) mice and examined the resulting pancre atic infiltrate by how cytometry. Two different V beta 4(+)CD4(+) T ce ll clones, BDC 2.5 and BDC 6.9, were found to recruit a heterogeneous T cell population as determined by staining with a panel of anti-TCR V beta monoclonal antibodies. The majority of the diabetes-initiating, V beta 4(+) T cell clones migrated to the spleen whereas only 5-8% of the T cell population infiltrating the pancreas was V beta 4(+). Anti- IL-2 receptor staining indicated that fewer than 10% of the total popu lation of infiltrating lymphocytes within the pancreas were in a highl y activated state. We have further found that normal splenic T cells f rom the NOD mouse proliferate poorly to IL-2 in vitro, yet secrete IFN -gamma in response to IL-2 stimulation. These results suggest that the recruited host T cells in our disease transfer system are not directl y pathogenic but, rather, are responding to the small numbers of infla mmatory T cell clones by providing cytokines that facilitate the disea se process. (C) 1998 Academic Press.