The effect of TCR Vβ8 peptide protection and therapy on T cell populations isolated from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis

Abstract

Vaccination or treatment of Lewis rats with TCR Vβ8 peptides can prevent or reverse the clinical signs of experimental autoimmune encephalomyelitis (EAE) which is mediated predominantly by Vβ8.2 + CD4 +/CD45R lo T cells. However, rats protected or treated with Vβ8 peptides still developed histological lesions in the spinal cord (SC), even though they remained clinical well. We sought to discern phenotypic changes characteristic of these SC infiltrating lymphocytes. In particular, we focused on whether the immunoregulatory mechanism induced by TCR peptides caused a reduction of Vβ8.2 + T cells, or induced changes in CD45R lo or hi/CD4 + subpopulations that have been associated respectively with EAE induction or recovery. In the Vβ8 peptide vaccinated rats there was a dramatic decrease in the number of Vβ8.2 + T cells isolated from the SC early in disease. During the recovery phase, however, the number of Vβ8.2 + SC T cells was similar in protected and control groups; in contrast, there was a striking reduction in the number and size of CD45R hi/CD4 + T cells in the protected animals. In rats treated with Vβ8.2 peptide, no changes were observed in the number of SC Vβ8.2 + T cells or expression of Vβ8.2 message, but similar to vaccinated rats, there was a marked decrease in the number of CD45R hi/CD4 + T cells. These data suggest that vaccination with TCR peptides prevented the initial influx of encephalitogenic Vβ8.2 + T cells into the central nervous system (CNS), whereas treatment appeared to inactivate Vβ8.2 + T cells already present in the CNS. In both cases, TCR peptide-induced inhibition of the encephalitogenic T cells apparently preempted the need for CD45R hi/CD4 + T cells that may normally be necessary to resolve the disease.