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 performed 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.
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2