Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28- T cells

Specific suppression of the host's immune response to donor HLA antigens remains the ultimate goal for clinical transplantation. In spite of considerable effort, however, allospecific human suppressor T cells (Ts) have been difficult to generate. Here we show that allospecific and xenospecific Ts can be raised by multiple priming of human T cells in mixed lymphocyte cultures. Ts derive from the CD8+CD28- subset and recognize specifically the MHC class I antigens expressed by antigen-presenting cells (APC) used for in vitro immunization. Allospecific Ts prevent the up-regulation of B7 molecules on target APC, interfering with the CD28-B7 interaction required for T helper (Th) activation. These findings provide a basis for the development of specific immunosuppressive therapy.