SPECIFIC SUPPRESSION OF T-HELPER ALLOREACTIVITY BY ALLO-MHC CLASS-I-RESTRICTED CD8(-) T-CELLS()CD28()

Specific suppression of the host's immune response to donor HLA antige ns remains the ultimate goal for clinical transplantation. In spite of considerable effort, however, allospecific human suppressor T cells ( T-s) have been difficult to generate. Here we show that allospecific a nd xenospecific T-s can be raised by multiple priming of human T cells in mixed lymphocyte cultures. T-s derive from the CD8(+)CD28(-) subse t and recognize specifically the MHC class I antigens expressed by ant igen-presenting cells (APC) used for in vitro immunization. Allospecif ic T-s prevent the up-regulation of B7 molecules on target APC, interf ering with the CD28-B7 interaction required for T helper (T-h) activat ion. These findings provide a basis for the development of specific im munosuppressive therapy.