THE ROLE OF B7 CO-STIMULATION IN ACTIVATION AND DIFFERENTIATION OF CD4(-CELLS() AND CD8(+) T)

The functional significance of B7 co-stimulation in T-cell activation was described first in the context of preventing the induction of aner gy. The functions of this pathway are far more complex than initially appreciated in view of the existence of two B7 molecules which have sp ecificities for both CD28 and CTLA-4, which serve to amplify and termi nate T-cell responses respectively. Mice lacking B7 co-stimulators and CD28 and CTLA-4 co-stimulatory receptors are helping to clarify the f unctions of this key immunoregulatory pathway. In this review we will focus on the role of B7 co-stimulation in the activation and different iation of CD4(+) helper cells and CD8(+) cytotoxic cells. The contribu tion of B7 co-stimulation to CD4(+) responses depends upon the derivat ion history of the T-cell and the strength of the T-cell antigen recep tor signal. B7 co-stimulation contributes to interleukin (IL)-2 produc tion by both naive and previously activated CD4(+) T cells. B7 co-stim ulation is most critical for the differentiation of naive CD4(+) T cel ls to IL-4 producers, but predominately influences IL-2 production by previously activated CD4(+) cells. B7 co-stimulation is important in d evelopment of cytotoxic T cells through both effects on T-helper cells and by direct co-stimulation of CD8(+) cells.