Synergistic effects of co-expression of the TH1 cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells

Int J Cancer. 1995 May 29;61(5):628-34. doi: 10.1002/ijc.2910610508.

Abstract

While the effect of cytokines on the generation of tumor-reactive cytotoxic cells has been a topic of active investigation, the effect of physiological cytokine combinations has not been determined. We have investigated the effect of co-expression of IL-2 and IFN-gamma on the generation of cytotoxic cells against the murine line 1 tumor in vivo. These cytokines were selected because they are normally produced in concert by a subset of T-helper cells called T-helper 1 (Th1). We transfected the line 1 murine carcinoma with cDNA for IL-2 and IFN-gamma, alone or combined. IFN-gamma alone does not elicit rejection of the transfectant, but IL-2 increases the tumorigenic dose by 10,000-fold above the parental cells. Co-expression of IFN-gamma and IL-2 increases this rejection to at least 100,000-fold above parental line 1. Unlike IL-2 transfectants, tumor cells expressing both IFN-gamma and IL-2 can also elicit rejection of admixed parental tumor cells. Finally, the IFN-gamma/IL-2 transfectants are more effective at generating memory cells that are cytolytic for the parental tumor. Our results show that synergistic interactions of Th1 cytokines can remarkably enhance the cytotoxic response to tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic*
  • Histocompatibility Antigens Class I / biosynthesis
  • Immunologic Memory
  • Interferon-gamma / pharmacology*
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Histocompatibility Antigens Class I
  • Interleukin-2
  • Interferon-gamma