Effect of interleukin 2 on cytotoxic effectors: I. short‐term culture of the cytotoxic effectors and the in vivo anti‐tumor activity of the cultured effectors isolated from tumor site

The effects of interleukin 2 (IL2) on the in vitro and in vivo activity of cytotoxic T cells have been studied. IL2 was produced by W/Fu rat spleen cells cultured with concanavalin A. The IL2 thus prepared gave an optimal T‐cell growth‐promoting effect at a concentration of 5–20% equivalents of the original preparation. In the primary, syngeneic mixed lymphocyte/tumor cell cultures (MLTC) against FBL‐3 tumor cells, the addition of IL2 failed to generate a cytotoxic response. However, the cytotoxic response could be generated in MLTC by addition of exogenous macrophages. On the other hand, IL2 could maintain the growth of preformed cytotoxic T cells for 3 to 5 weeks. These cytotoxic T cells were generated either by in vitro sensitization (MLC or MLTC) or by in vivo sensitization of B6 mice against a syngeneic tumor FBL‐3. In short‐term cultures, augmentation of the cytotoxic activity was seen after 10 days' culturing with IL2. The antigenic specificity of the cytotoxic reaction was altered after 28–35 days in culture, and the effectors broadly reactive. When growing a nonadherent population of lymphocytes isolated from FBL‐3 ascites tumor, supplementation with IL2 selectively promoted the growth of a T‐cell population, resulting in the elimination of the contaminating tumor cells. These purified T cells were highly cytotoxic for FBL‐3 cells in vitro and also possessed strong in vivo anti‐tumor activity against FBL‐3 cells in the adoptive transfer experiments. The present study demonstrates that short‐term culture (2–3 weeks) in IL2 promotes the growth of T cells and augments their cytotoxic activity with the appropriate antigenic specificity. IL2 also promoted the selective growth of T cells isolated from tumor site and these T cells showed augmented in vitro and in vivo anti‐tumor activity.