[CITATION][C] New perspectives of C1328-137-mediated T cell costimulation

JA Bluestone - Immunity, 1995 - Elsevier
Immunity, 1995Elsevier
Recent findings indicate that the regulation of costimulation mediated by the CD2EB7
system is far more complex than previously appreciated. First, although CDP&mediated
costimulation is necessary to prevent the induction of anergy in Thl T cell clones, the primary
effect of CD28-mediated costimulation of resting T cells is to promote late cell cycle
progression by maximizing IL-2 production and regulating programmed cell death. CD28
blockade of primary T cell activation does not induce anergy, as has been found with Thl …
Recent findings indicate that the regulation of costimulation mediated by the CD2EB7 system is far more complex than previously appreciated. First, although CDP&mediated costimulation is necessary to prevent the induction of anergy in Thl T cell clones, the primary effect of CD28-mediated costimulation of resting T cells is to promote late cell cycle progression by maximizing IL-2 production and regulating programmed cell death. CD28 blockade of primary T cell activation does not induce anergy, as has been found with Thl clones. Second, at least two molecules, 87-l and 87-2, can function as costimulatory ligands for CD28. However, 87-2 appears to be the dominant costimulatory ligand during primary immune responses, whereas 87-1, which is up-regulated later in immune responses, may be critical in prolonging primary T cell responses or costimulating secondary T cell responses. Third, the CD28 homolog, CTLA-4, functions to downregulate immunity by binding with high affinity to B7family members. And finally, under certain conditions, T cells can be activated in a CD28-independent manner. T cell activation can be CD28 independent as a result of engagement of alternative costimulatory pathways or high potency TCR ligation. This review will summarize current studies that address the complexity of CD28 costimulation and propose a model for CD28 costimulation based on the premise that CD28 ligation acts synergistically with TCR ligation to maximize T cell signaling, promote cell differentiation/expansion, and, as a consequence, regulate the balance of inflammatorylhumoral(Thl/Th2) responses during an immune reaction.
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