CORTICOSTEROID TREATMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITISIN THE LEWIS RAT RESULTS IN LOSS OF V-BETA-8.2(-REACTIVE CELLS FROM THE SPINAL-CORD, WITH INCREASED TOTAL T-CELL APOPTOSIS BUT REDUCED APOPTOSIS OF V-BETA-8.2(+) CELLS() AND MYELIN BASIC PROTEIN)

We have studied the effects of corticosteroid treatment on the numbers of lymphocytes obtained from the spinal cords of Lewis rats with acut e experimental autoimmune encephalomyelitis (EAE) induced by inoculati on with myelin basic protein (MBP) and adjuvants. Flow cytometric stud ies showed that treatment with dexamethasone (4 mg/kg) 8-12 h prior to study on day 14 after inoculation resulted in a reduction in the numb ers of CD5(+), TCR alpha beta(+) and V beta 8.2(+) cells in the spinal cord. Limiting dilution analysis indicated that dexamethasone treatme nt 12 h prior to study on day 12 after inoculation reduced the frequen cies of MBP-reactive and interleukin-2-responsive lymphocytes in the s pinal cord to low levels, but reduced the frequency of concanavalin-A- responsive lymphocytes to a lesser extent. Using propidium iodide stai ning of nuclear chromatin we also studied lymphocyte apoptosis. Greate r numbers of apoptotic cells were found in the cells extracted from th e spinal cords of rats, examined on day 14, that had been treated 1-12 h previously with dexamethasone, than in saline-treated controls. Thi s increased level of apoptosis was observed in the CD5(+) and TCR alph a beta(+) cell populations. At 1-4 h after dexamethasone treatment the re was a reduction in the selective apoptosis of V beta 8.2(+) cells t hat normally occurs during spontaneous recovery from EAE. Therefore ap optosis of V beta 8.2(+) cells cannot explain the reduction in the num bers of V beta 8.2(+) cells and MBP-reactive cells in the CNS after de xamethasone treatment. By 8-12 h after dexamethasone treatment the sel ectivity of the apoptotic process was restored. These studies suggest that a reduction in the number of T-lymphocytes in the central nervous system contributes to the beneficial effects of corticosteroids in EA E.