T-T CELLULAR INTERACTION BETWEEN CD4(-)CD8(-) REGULATORY T-CELLS AND T-CELL CLONES PRESENTING TCR PEPTIDE - ITS IMPLICATION FOR TCR VACCINATION AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Regulatory T cells recognizing TCR determinants presumably play a crit ical role in the control of experimental autoimmune encephalomyelitis, a prototype tissue-specific autoimmune disease. This study was initia ted to determine whether regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50-68) in SJL/J mice. Although the TC R peptide showed regulatory effects in vivo, the presence of T cells s pecific for the peptide could not be proven with conventional prolifer ation assays. Unexpectedly, in the presence of myelin basic protein-sp ecific T clone cells (Tcc), the sensitized spleen cells vigorously pro liferated in response to the TCR peptide, The subsequent experiment sh owed that this was due to the outstanding capability of the Tcc as APC for the exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta 17a(50-68)-specific T cell lines from in vivo primed spleen cells. The line cells were MHC class I restricted and dominated by T cells with a distinct surface phenotype (CD4(-)CD8(-)V beta 17a( +)). Presentation of the peptide by the Tcc was inhibited by treatment with gelonin that could block a MHC class I presentation pathway. The ability of T cells to present the TCR peptide was not related to thei r Ag specificity, but correlated with the expression levels of MHC cla ss I molecules and adhesion molecules such as intercellular adhesion m olecule-1 and B7-1 on their surface. The TCR peptide-specific T cells produced a soluble mediator(s) that is inhibitory for T cell activatio n and were protective against actively induced experimental autoimmune encephalomyelitis. These results show that V beta 17a(50-68) vaccinat ion induces regulatory CD4(-)CD8(-) T cells that could interact with T cells presenting relevant TCR fragments.