Production of interleukin-6 in vitro parallels development of cytotoxic T lymphocytes from murine thymocytes.
In an attempt to provide information useful for improving tumor immunotherapy, we examined the lymphokine requirements for generation of cytotoxic T lymphocytes (CTL) from C57BL/6 murine thymocytes. Our previous work indicated that interleukin-6 (IL-6) is involved in the maturation of CTL in vitro. Using a standard chromium 51 release assay and P815 mastocytoma tumor cells as targets, we found that after 66 hours of in vitro culture, a much greater CTL response was generated in the presence of interleukin-2 (IL-2) plus IL-6 (70.5% +/- 10.6%) compared with that generated in the presence of IL-2 only (25.2% +/- 1.0%). After 72 hours of culture, however, this difference was no longer significant, with cultures incubated with both IL-2 and IL-6 yielding 70.6% +/- 1.8% lysis versus 64.5% +/- 3.4% for cultures incubated with IL-2 only. To attempt to understand this difference, we examined the production of IL-6 in thymocyte cultures using a cell line, PC-6, that proliferates in the presence of IL-6. We found that the CTL response generated from unfractionated murine thymocytes in the presence of concanavalin A plus IL-2 correlated with production of IL-6 by cells within the thymic population. These data suggest that the generation of a CTL response in the absence of added IL-6 is due to the production of this ubiquitous lymphokine by thymocytes on in vitro culture. We present this as further evidence that IL-6 is necessary for the development of functional CTL from murine thymocytes and may therefore play a role in the development of effective tumor immunotherapy.
Stringfellow
M M
MM
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Wilson
R E
RE
Herrmann
S H
SH
D000818:Animals; D002478:Cells, Cultured; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins