The Role of B7-1 and LFA-3 in Costimulation of CD8⁺ T Cells

This study compares the ability of LFA-3 (CD58) and B7-1 (CD80) ligands to provide costimulatory signals for superantigen (SAg)-stimulated CD8⁺ and CD4⁺ T cells. We show that B7-1 and LFA-3 costimulation activate CD8⁺ T cells to proliferation, cytokine production (IL-2, TNF, and IFN-γ), and cytotoxicity. A long-lasting proliferative response was observed after combined DR/B7-1/LFA-3 costimulation. Detailed analysis of SEA-activated CD8⁺ T cells revealed that maximal production of IFN-γ was seen in LFA-3-costimulated cells, while production of IL-2 was mainly induced after B7-1 costimulation. A fivefold increase in the IFN-γ production was observed when activated CD8⁺ T cells were costimulated with Chinese hamster ovary (CHO)-DR/ LFA-3 cells compared with the secretion induced by CHO-DR/B7-1. In contrast, SEA-treated CD4⁺ T cells costimulated with B7-1 or LFA-3 gave rise to a similar production of IFN-γ, suggesting a preferential function for the CD2/LFA-3 pathway in the regulation of IFN-γ in CD8⁺ T cells. Moreover, the generation of CTL was supported similarly by B7-1 and LFA-3 costimulation, but not by CHO-DR cells. We conclude that ligation of the CD28 and CD2 receptors mediate distinct effect on CD8⁺ and CD4⁺ T cell effector functions.