T-CELL COSTIMULATORY PATHWAYS - PROMISING NOVEL TARGETS FOR IMMUNOSUPPRESSION AND TOLERANCE INDUCTION

It is now accepted that T cells need two signals for full activation. The first is the foreign antigen itself presented by self-major histoc ompatibility complex and thus provides antigen specificity to the immu ne response. The second is a ''costimulatory'' signal, the best-charac terized of which is provided through the T cell accessory molecule CD2 8. In vitro, the blockade of costimulatory signals inhibits T cell act ivation and induces a state of antigen-specific unresponsiveness. In v ivo, agents that block CD28-mediated costimulation have proved extreme ly effective in inhibiting the immune response in experimental models of transplantation and autoimmune disease, providing novel strategies for use in clinical trials in the near future.