THE EFFECT OF TCR V-BETA-8 PEPTIDE PROTECTION AND THERAPY ON T-CELL POPULATIONS ISOLATED FROM THE SPINAL-CORDS OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Vaccination or treatment of Lewis rats with TCR V beta 8 peptides can prevent or reverse the clinical signs of experimental autoimmune encep halomyelitis (EAE) which is mediated predominantly by V beta 8.2(+) CD 4(+)/CD45R lo T cells. However, rats protected or treated with V beta 8 peptides still developed histological lesions in the spinal cord (SC ), even though they remained clinically well. We sought to discern phe notypic changes characteristic of these SC infiltrating lymphocytes. T n particular, we focused on whether the immunoregulatory mechanism ind uced by TCR peptides caused a reduction of V beta 8.2(+) T cells, or i nduced changes in CD45R lo or hi/CD4(+) subpopulations that have been associated respectively with EAE induction or recovery. In the V beta 8 peptide vaccinated rats there was a dramatic decrease in the number of V beta 8.2(+) T cells isolated from the SC early in disease. During the recovery phase, however, the number of V beta 8.2(+) SC T cells w as similar in protected and control groups; in contrast, there was a s triking reduction in the number and size of CD45R hi/CD4(+) T cells in the protected animals. In rats treated with VP beta 8.2 peptide, no c hanges were observed in the number of SC V beta 8.2(+) T cells or expr ession of V beta 8.2 message, but similar to vaccinated rats, there wa s a marked decrease in the number of CD45R hi/CD4(+) T cells. These da ta suggest that vaccination with TCR peptides prevented the initial in flux of encephalitogenic V beta 8.2(+) T cells into the central nervou s system (CNS), whereas treatment appeared to inactivate V beta 8.2(+) T cells already present in the CNS. In both cases, TCR peptide-induce d inhibition of the encephalitogenic T cells apparently preempted the need for CD45R hi/CD4(+) T cells that may normally be necessary to res olve the disease.