Abstract
THE receptor–ligand pairs CD28–B7 and CD40–gp39 are essential for the initiation and amplification of T-cell-dependent immune responses1,2. CD28–B7 interactions provide 'second signals' necessary for optimal T-cell activation and IL-2 production3–5, whereas CD40–gp39 signals co-stimulate B-cell, macrophage, endothelial cell and T-cell activation6–12. Nonetheless, blockade of either of these pathways alone is not sufficient to permit engraftment of highly immunogenic allografts13–15. Here we report that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts. The requirement for simultaneous blockade of these pathways for effective inhibition of alloimmunity indicates that, although they are interrelated, the CD28 and CD40 pathways are critical independent regulators of T-cell-dependent immune responses.
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Larsen, C., Elwood, E., Alexander, D. et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381, 434–438 (1996). https://doi.org/10.1038/381434a0
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DOI: https://doi.org/10.1038/381434a0
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