CYTOKINE-INDEPENDENT PROLIFERATION OF IL-2-NONPRODUCING CTL CLONES INASSOCIATION WITH HIGH TCR-SIGNAL TRANSDUCTION RESPONSES

Alloreactive CTL clone D2-23 proliferated in response to antigenic cel ls without IL-2 production. Among subclones of D2-23, the F1 but not F 2 done proliferated in response to soluble aCD3 or PMA, although both clones proliferated in response to immobilized aCD3, antigenic cells o r soluble aCD3 plus costimulatory cells. The difference in responsiven ess between F1 and F2 was not caused by distinct expression of CD3 or Fc receptors. Cyclosporin A, which totally blocks IL-2 production of T h1 cells, barely or only partially inhibited PMA- or aCD3-induced prol iferation of F1. F1 did not produce cytokines for proliferation of F2 in response to soluble aCD3, Tyrosine phosphorylation developed for va rious proteins of F1 and F2 at the levels apparently correlated to the extent of cell proliferation when the cells were stimulated with solu ble aCD3 or PMA. The proliferative responsiveness of F1 and F2 to the described stimulators was maintained by stimulation with IL-2 plus ant igenic cells, or even IL-2 alone, but was decreased during resting cul ture or by stimulation with immobilized aCD3. These results show evide nce of a new TCR-linked mechanism for CTL proliferation that is indepe ndent of costimulatory cell- or cytokine-mediated signaling, but is or iginally prepared by prior stimulation with IL-2.