Modulating co-stimulation |
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Authors: | Vissia Viglietta Samia J Khoury |
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Institution: | (1) Kathleen B and Mason I Lowance Center for Human Immunology and Rheumatology, Emory University, 30322, Woodruff Circle, Atlanta, Georgia, USA |
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Abstract: | 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. |
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