CD28/B7 costimulation: a review

Crit Rev Immunol. 1998;18(5):389-418. doi: 10.1615/critrevimmunol.v18.i5.10.


The current model of T cell activation requires two signals. The first signal is specific, requiring T cell receptor recognition and binding to MHC/Antigen presented by an antigen-presenting cell. The second signal is nonspecific, resulting from the binding of B7 ligand on the antigen-presenting cell with its receptor, CD28, on the T cell. If both signals are provided, the T cell will proliferate and secrete cytokines. Recently, it has been shown that CTLA4, another receptor for B7 that is upregulated following T cell after activation, can deliver an inhibitory signal, downregulating T cell proliferation. The B7 family of ligands has two family members, B7-1 and B7-2. They both bind to CD28 and CTLA4, but they differ in their binding affinity, structure, and temporal expression. Considerable research has been done on the CD28/B7 costimulatory pathway. Different ways of manipulating this pathway could provide insights into the mechanism and treatment of opposing pathological states. Blocking the CD28/B7 pathway could result in immunosuppression, with implications for the treatment of autoimmune diseases, organ transplantation, and graft vs. host disease. Activating the CD28/B7 pathway could be useful for including the immune system to recognize and eliminate tumors that evade the immune system. Finally, the CD28/B7 pathway could be involved with maintaining immune tolerance, as recent studies suggest the preferential binding of the B7-CTLA4 pathway results in the down-regulation of the responding T cells. Thus, the B7/CD28/CTLA4 pathway has the ability to both positively and negatively regulate immune responses.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Autoimmune Diseases
  • B7-1 Antigen / immunology*
  • B7-1 Antigen / metabolism
  • CD28 Antigens / immunology*
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen
  • Cell Differentiation
  • Clonal Anergy
  • Humans
  • Immunoconjugates*
  • Lymphocyte Activation*
  • Neoplasms / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Transplantation Immunology


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