CD28/B7 costimulation: a review

EA Greenfield, KA Nguyen… - Critical Reviews™ in …, 1998 - dl.begellhouse.com
Critical Reviews™ in Immunology, 1998dl.begellhouse.com
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 …
Abstract
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.
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