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

Abstract

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 (T(s)) have been difficult to generate. Here we show that allospecific and xenospecific T(s) can be raised by multiple priming of human T cells in mixed lymphocyte cultures. T(s) derive from the CD8+ CD286- subset and recognize specifically the MHC class I antigens expressed by antigen-presenting cells (APC) used for in vitro immunization. Allospecific T(s) prevent the up-regulation of B7 molecules on target APC, interfering with the CD28-B7 interaction required for T helper (T(h)) activation. These findings provide a basis for the development of specific immunosuppressive therapy.