The clinical utility of inhibiting CD28-mediated costimulation

Immunol Rev. 2009 May;229(1):307-21. doi: 10.1111/j.1600-065X.2009.00780.x.


This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • CD28 Antigens / drug effects*
  • CD28 Antigens / immunology*
  • CTLA-4 Antigen
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Humans
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Organ Transplantation
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*


  • Antigens, CD
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept