EFFECTS OF ORAL TOLERANCE INDUCTION BY MYELIN BASIC-PROTEIN ON V-BETA-8-CELLS( LEWIS RAT T)

Encephalitogenic T cells from Lewis rats use a restricted T cell recep tor (TCR) gene combination, V beta 8.2 and V alpha 2., The oral admini stration of myelin basic protein (MBP) to Lewis rats prior to encephal itogenic challenge results in a marked inhibition of clinical neurolog ic signs of encephalitis, reduced central nervous system pathology, su ppressed T cell reactivity to MBP, and decreased serum anti-MBP antibo dy responses, The present study determined the TCR V beta 8 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 ch ain V region probe positive for V beta 8.2. The results indicate that feeding MBP results in a decrease in V beta 8+ TCR RNA expression in l ymph nodes draining the site of encephalitogenic challenge, T cell pro liferation was reduced in LNC of tolerized rats relative to control ra ts, No change in the V beta 8+ TCR RNA expression or MBP reactivity wa s observed in the mesenteric lymph nodes (MLN) of vehicle-fed or MBP-f ed rats, although an increase in cell number was found in the MLN of b oth groups, These results suggest that the mechanisms of orally induce d tolerance involve local clonal deletion or migration of V beta 8+ T cells, of which MBP-specific T cells are a part, (C) 1998 Wiley-Liss, Inc.