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International Immunology, Vol 10, 775-783, Copyright © 1998 by Oxford University Press

ARTICLES

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

Z Liu, S Tugulea, R Cortesini and N Suciu-Foca
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York, NY 10032, USA.

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.
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