The evolution of the immunobiology of co-stimulatory pathways: clinical implications

Co-stimulatory pathways are a prerequisite for the regulation of T-cell activation and tolerance. After the engagement of the T-cell receptor (TCR) to the major histocompatibility complex (MHC)/peptide complex, the co-stimulatory signals are critical to decide the outcome of the immune response. While positive co-stimulatory signals promote T-cell activation, negative signals delivered through inducible co-inhibitory receptors limit immune response, thereby regulating tolerance and autoimmunity. This review is intended not only to give an overview of the immunobiology of co-stimulatory pathways and their role in autoimmune diseases, but will also highlight the complexities and relevant issues one may have to think through to translate the target-ing of co-stimulatory pathways into successful therapeutic interventions.