SPECIFIC SUPPRESSION OF HUMAN CD4(-) REGULATORY T-CELLS() TH CELL RESPONSES TO PIG MHC ANTIGENS BY CD8(+)CD28()

Evidence that T cells can down-regulate the immune response by produci ng or consuming certain cytokines or by lysing APCs or Th cells has be en provided in various systems. However, the generation and characteri zation of suppressor T cell lines have met with limited success. Here we show that xenospecific suppressor T cells can be generated by in vi tro stimulation of human T cells with pig APCs, Similar to allospecifi c suppressors, these xenospecific suppressor T cells carry the CD8(+)C D28(-) phenotype and react to MHC class I Ags expressed by the APCs us ed for priming. TCR spectratyping of T suppressor cells showed oligocl onal usage of TCR-VB families, indicating that xenostimulation of CD8( +)CD28(-) T cells results in Ag-driven selection of a limited VP reper toire. Xenospecific T suppressor cells prevent the up-regulation of CD 154 molecules on the membrane of Th cells, inhibiting their ability to react against the immunizing MHC class TI xenoantigens, The mechanism of this suppression, therefore, appears to be blockade of CD154/CD40 interaction required for efficient costimulation of activated T cells.