TARGET ORGAN-SPECIFIC UP-REGULATION OF THE MRC OX-40 MARKER AND SELECTIVE PRODUCTION OF TH1 LYMPHOKINE MESSENGER-RNA BY ENCEPHALITOGENIC T-HELPER CELLS ISOLATED FROM THE SPINAL-CORD OF RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Lewis X Buffalo F-1 rat lymphocytes express both forms of the allelic marker RT7.1 (Lewis) and RT7.2 (Buffalo). We generated myelin basic pr otein (MBP)-specific encephalitogenic F-1 T helper cell lines and adop tively transferred them into naive irradiated Lewis recipients, which enabled us to detect and isolate donor T cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid (CSF) were highly enriched for the donor T cells compared with the blood and spleen. Th e donor cell number peaked on the first day of disease in the spinal c ord and CSF and decreased as the disease progressed. A high percentage of the donor T cells isolated from the spinal cord were positive for the T helper cell activation marker OX-40, whereas a (lower) percentag e of CSF donor cells expressed OX-40. Donor cells isolated from blood or spleen were negative for OX-40 expression. In contrast, the IL-2 re ceptor (CD25) was positive on all the transferred T cells in all tissu e sites examined. Cell-sorting experiments showed that the MBP-specifi c donor cells were enriched for IFN-gamma, IL-2, TNF-alpha, and IL-3 m RNA when compared with the host-recruited spinal cord cells, whereas s imilar amounts of IL-10 mRNA were produced by both populations. Lympho kine mRNA production was also enriched in donor T cells isolated from the spinal cord compared with donor T cells isolated from the spleen. The spinal cord donor cells produced higher levels of IL-2, IFN-gamma, and IL-3 mRNA, whereas similar amounts of IL-10 and TNF-alpha mRNA we re produced from donor cells isolated from the spleen and the spinal c ord. Our data suggest that the amount/percentage, activation state, an d enhanced lymphokine production at the site of inflammation are all i mportant factors in determining the autoimmune potential of Ag-specifi c effector T helper cells.