Abstract

T cell activation requires two signals: a signal from the TCR and a co‐stimulatory signal provided by antigen‐presenting cells (APC). In addition to CD28, multiple molecules on the T cell have been described to deliver co‐stimulatory signals. Here, we investigated whether there exist quantitative or qualitative differences in the co‐stimulatory capacity between CD28 and other molecules. Anti‐CD28 monoclonal antibody (mAb) and mAb against CD5, CD9, CD2, CD44 or CD11a all induced activation of naive T cells in the absence of APC when co‐immobilized with a submitogenic dose of anti‐CD3 mAb. [ 3 H]Thymidine incorporation determined 2 days after co‐stimulation was all comparable. In contrast to progressive T cell proliferation induced by CD28 co‐stimulation, co‐stimulation by other T cell molecules led to a decrease in viable cell recovery along with the induction of apoptosis of once activated T cells. This was associated with a striking difference in IL‐2 production; CD28 co‐stimulation induced progressively increasing IL‐2 production, whereas co‐stimulation by other molecules produced limited amounts of IL‐2. Addition of recombinant IL‐2 to the latter cultures corrected the induction of apoptosis, resulting in levels of cellular proliferation comparable to those observed for CD28 co‐stimulation. These results indicate that a fundamental difference exists in the nature of co‐stimulation between CD28 and other molecules, which can be evaluated by the levels of IL‐2 production, but not simply by [ 3 H]thymidine incorporation.