Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6.
Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synergistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB/c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against 51Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.
Ford
H R
HR
Department of Surgery, University of Pittsburgh, PA.
Hoffman
R A
RA
Wang
S
S
Simmons
R L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D003208:Concanavalin A; D015847:Interleukin-4