Either B7 costimulation or IL-2 can elicit generation of primary alloreactive CTL

B7-1 and B7-2 are important costimulatory molecules in the activation of T cell immunity. We have used mice made genetically deficient in either or bo th B7 molecules to determine the role of B7 molecules in activation of prim ary alloreactive CTL, The absence of either B7-1 or B7-2 did not alter gene ration of CTL from unfractionated lymphocytes, but the absence of B7-2 grea tly decreased CTL generation from purified CD8(+) responder cells. However, if B7-1 was induced on the stimulating cells then CTL generation was resto red to wild-type levels. Absence of both B7-1 and B7-2 from MLR using whole splenocytes resulted in a profound reduction in generation of CTL, This co uld completely be reversed by the addition of IL-2, B7 molecules could dire ctly costimulate CD8(+) cells, as purified CD8(+) cells developed into matu re CTL when stimulated with wild-type APC, but not with B7-deficient APC, A gain, IL-2 could drive CTL generation from purified CD8(+) cells, even in t he absence of B7 molecules, Taken together, these results demonstrate an im portant role for B7 costimulation in CTL generation.