Effects of oral tolerance induction by myelin basic protein on Vbeta8+ Lewis rat T cells.

Abstract

Encephalitogenic T cells from Lewis rats use a restricted T cell receptor (TCR) gene combination, Vbeta8.2 and Valpha2. The oral administration of myelin basic protein (MBP) to Lewis rats prior to encephalitogenic challenge results in a marked inhibition of clinical neurologic signs of encephalitis, reduced central nervous system pathology, suppressed T cell reactivity to MBP, and decreased serum anti-MBP antibody responses. The present study determined the TCR Vbeta8 gene usage in rats rendered orally tolerant to MBP as compared with vehicle-fed or unfed controls. Total RNA was extracted from lymph node cells (LNC), Northern blots run, and hybridizations performed using a rat beta chain V region probe positive for Vbeta8.2. The results indicate that feeding MBP results in a decrease in Vbeta8+ TCR RNA expression in lymph nodes draining the site of encephalitogenic challenge. T cell proliferation was reduced in LNC of tolerized rats relative to control rats. No change in the Vbeta8+ TCR RNA expression or MBP reactivity was observed in the mesenteric lymph nodes (MLN) of vehicle-fed or MBP-fed rats, although an increase in cell number was found in the MLN of both groups. These results suggest that the mechanisms of orally induced tolerance involve local clonal deletion or migration of Vbeta8+ T cells, of which MBP-specific T cells are a part.