Brief Definitive Report Dissection of the Proliferative and Differentiative Signals Controlling Murine Cytotoxic T Lymphocyte Responses* Il-2-producing Tlymphoma Cells. the Il-2-producing Ei~ Variant (13) Was Kindly Provided

The induction of antigen-specific primary cytotoxic T lymphocyte (CTL) responses in vitro clearly requires interactions between several cell types and soluble mediators (1-5). One essential interaction occurs between the Lyt-2 + C T L precursor (CTL-P) and an antigen-activated Lyt-1 + helper T cell (6-8). This interaction is considered to occur by way of soluble mediator such as interleukin 2 (IL-2), a lymphokine produced by antigen-triggered helper cells that binds to IL-2 receptors expressed on CTL-P as a sequel to their preactivation by antigen or mitogen (9, 10). The expression of IL-2 receptors probably occurs as antigenor mitogen-triggered CTL-P move from Go to G1 in the cell cycle (11). Further progress through the cell cycle, then, only occurs if IL-2 is present. However, whereas IL-2 may indeed drive an antigenor mitogenpreactivated CTL-P into proliferation, it is not clear whether IL-2 is also the stimulus that causes the CTL-P to differentiate into effector CTL. This uncertainty exists because the source of IL-2 used by most investigators to study its role in C T L induction comes from concanavalin A (Con A) supernatants, which contains other biologically active molecules as well. We realized that IL-2 alone may not be sufficient to mature cells into C T L in preliminary experiments in which certain sources of IL-2 were shown capable of driving Con A-preactivated Lyt-2 + cells to proliferation but not differentiation into C T L (12). However, as we show in this communication, IL-2 preparations unable to cause C T L differentiation can be reconstituted with Con A supernatants that have been selectively depleted of their IL-2 content. As such, our results are the first to provide evidence for the existence of a cytotoxic T cell differentiation factor (CTDF) that functions to convert IL-2-driven proliferating CTL-P into CTL.