Modulating co-stimulation.
The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4+ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing auto-antigen driven T-cell activation in humans with particular attention to the CD28/B7 pathway. Inhibiting co-stimulatory molecule interactions by using monoclonal antibodies seems to be an original approach to regulate autoimmune diseases in humans.
Viglietta
Vissia
V
Clinical Immunology Laboratory, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. vviglietta@rics.bwh.harvard.edu
Khoury
Samia J
SJ
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D018106:CD28 Antigens / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D018448:Models, Immunological; D015398:Signal Transduction
D018106:CD28 Antigens; D015704:CD4 Antigens