Blocking costimulatory signals to induce transplantation tolerance and prevent autoimmune disease.
Similar cellular and molecular mechanisms are responsible for the pathogenesis of transplant rejection and autoimmunity. Recent advances in the studies of lymphocyte activation have shown a requirement for two distinct signals for full activation and development of effector function. The first signal is antigen itself; the second is a nonspecific costimulatory signal, the best example of which is delivered through the CD28 receptor. We and others have shown that blockade of this costimulatory signal can be used as part of strategy to prevent or treat transplant rejection and autoimmune disorders in animal models. This paper will review these findings and discuss their implications for clinical use.
Khoury
S
S
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Sayegh
M H
MH
Turka
L A
LA
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D001327:Autoimmune Diseases / Q000517:prevention & control*; D018106:CD28 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D000069594:Abatacept