CD28-MEDIATED COSTIMULATION IS NECESSARY FOR OPTIMAL PROLIFERATION OFMURINE NK CELLS

CD28, a cell surface molecule expressed on all murine T cells, plays a critical role in T cell activation. We show here that NK-1.1(+) cells , a subpopulation of SCID splenocytes, and IL-2-activated NK cells exp ress CD28, although at lower levels than alpha beta T cells. Optimal p roliferation of highly purified asialo GM1(+) NK cells from the SCID s pleen was observed in response to stimulation with IL-2 and PMA, toget her with, anti-CD28 or L-B7(+) cells. Thus, in addition to IL-2, murin e NK cells require CD28-mediated costimulatory signals for optimal pro liferation. IL-2-activated NK cells produced enhanced levels of IFN-ga mma and TNF in response to stimulation with anti-CD28 and PMA. On the other hand, we were unable to demonstrate that CD28 signaling had any effect on NK-mediated cytotoxicity. We conclude that the CD28 costimul atory pathway is functional in NK cells and plays an important role in their proliferation and cytokine production.