Secondary murine cytotoxic T lymphocyte responses from alloantigen-primed T cells can be induced in vitro by apparently unrelated regimens, such as addition of either concanavalin A (Con A), conditioned medium from Con A stimulated lymphocyte cultures, conditioned medium from secondary mixed lymphocyte cultures (MLC), or stimulator cells sharing only the I-region with the stimulating cells used for primary sensitization. We now report that upon polyclonal (Con A), or antigen-specific (MLC) stimulation, Lyl+ T cells release a factor, which in turn triggers alloantigen primed Ly23+ T cells to proliferation and cytolytic activity. The secondary cytotoxic T lymphocyte inducing factor (SCIF) is produced within 24 h. For its production, an intact protein metabolism, not DNA metabolism, is required. Once induced, the functional activity of SCIF is nonspecific and not H-2 restricted. SCIF allows exponential growth and long-term propagation of cytolytic Ly23+ T cells with specificity to alloantigens used for primary sensitization. SCIF induced activation of alloantigen primed Ly23+ T cells does not require the presence of alloantigens. The results therefore reveal a process by which Lyl+ T-cell-derived nonspecific factor(s) induce autonomously Ly23+ T-cell-mediated, antigen-specific, cytotoxic T lymphocyte responses.

Differentiation of dispersed mouse thymus cells into cytotoxic lymphocytes has been shown for t h e first time to occur in an in vitro allograft system. It is concluded that t h e generation of cell-mediated cytotoxicity is a T cell phenomenon with no thymus-bone marrow synergism being required.

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The role of Lyt 1+ T-cell-derived secondard CTL inducing factor allowed the cloning of alloreactive cytotoxic T lymphocytes (CTL) by the limiting dilution approach. Several monoclonal cell lines were established in vitro. The lytic activity of some of the cell lines exceeded that of CTL from bulk cultures; that is, 50% of the target cells were lysed at an effector to target cell ratio of 0.04:1. The fine specificity of individual CTL clones is discussed.