COSTIMULATION REGULATES THE KINETICS OF INTERLEUKIN-2 RESPONSE TO BACTERIAL SUPERANTIGENS

The aim of this study was to investigate the mechanisms by which B7-re lated costimulatory molecules (CD80, CD86) increase T-cell responsiven ess to extracellular ligands. As a model study, the in vitro response of purified splenic CD4(+) T cells to a bacterial superantigen, SEE, w as characterized. Previous analysis of this experimental model led us to conclude that expression of B7-related molecules is strictly requir ed in order to activate CD4(+) T cells in the presence of bacterial su perantigens. In the present report, we demonstrate that antigen-presen ting cell-derived costimulatory signals regulate the kinetics of inter leukin-2 (IL-2) production by SEE-activated splenic CD4(+) T cells. In deed, experiments performed with purified subpopulations of antigen-pr esenting cells and using B7-transfected cell lines indicated that incr eased levels of CD80 and/or CD86 cell surface expression is associated with a Faster kinetics of IL-2 production in response to SEE. Accordi ngly, blocking of CD80 or CD86-derived signals by specific monoclonal antibodies led to a slower kinetics of IL-2 production in response to SEE. Thus these data demonstrate that similar strength of signal throu gh the T-cell receptor can lead to immune responses displaying distinc t kinetics depending on the level of costimulatory ligands on APC.