Effect of timing of lymphokine presentation on generation of cytotoxic T lymphocytes

M. M. Stringfellow, R. E. Wilson, S. J. Burakoff and S. H. Herrmann
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.

Encouraging results of clinical trials with interleukin 2 therapy for advanced malignant neoplasms have led to efforts to reduce the toxicity and improve the efficacy of tumor immunotherapy. To begin to achieve this goal, we studied the lymphokine requirements for in vitro generation of polyclonal cytotoxic T lymphocytes (CTL) from C57BL/6 murine thymocytes. We found that both interleukin 2 and interleukin 6 are required for optimal generation of CTL from murine thymocytes. Timing studies show that neither lymphokine alone in culture will produce maximum CTL levels during the first 84 hours of culture. In addition, we found that thymocytes cultured with concanavalin A are unresponsive unless either interleukin 2 or interleukin 6 is present from the onset of culture.