CD28-Specific Immunomodulating Antibodies: What Can Be Learned From Experimental Models?
Article first published online: 4 APR 2012
© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 12, Issue 7, pages 1682–1690, July 2012
How to Cite
Poirier, N., Blancho, G. and Vanhove, B. (2012), CD28-Specific Immunomodulating Antibodies: What Can Be Learned From Experimental Models?. American Journal of Transplantation, 12: 1682–1690. doi: 10.1111/j.1600-6143.2012.04032.x
- Issue published online: 28 JUN 2012
- Article first published online: 4 APR 2012
- Received 23 January 2012, revised 13 February 2012 and accepted for publication 14 February 2012
- immune tolerance;
- kidney transplantation;
- regulatory T cells
Tolerance induction to alloantigens remains a major challenge in transplant immunology. Progress in the last decade of our understanding of T-cell activation has led to the development of new immunotherapeutic strategies to replace conventional immunosuppression which inhibits the immune system in a nonspecific way. In particular, positive and negative costimulatory molecules of the CD28 family have been consistently demonstrated to be critical for the development of productive immune responses as well as the establishment and maintenance of peripheral tolerance. However, recent discoveries of novel costimulatory interactions confer a novel dimension to the immunoregulatory interactions within the B7:CD28 family and compels a revised view within a “quintet” of costimulatory molecules: CD28/B7/CTLA-4/PD-L1/ICOSL. Complexity introduced in this more detailed costimulatory pathway has important implications in therapeutic interventions against human immunological diseases and, especially, highlight the fundamental differences in selectively targeting CD28 molecules instead of B7 counterparts. In this review, we discuss these differences and emphasize different CD28-specific immunomodulating strategies evaluated in experimental models of transplantation and autoimmune diseases.