Analysis of the effect of cytokines (interleukins 2, 3, 4, and 6, granulocyte-monocyte colony-stimulating factor, and interferon-gamma) on generation of primary cytotoxic T lymphocytes against a weakly immunogenic tumor

Cell Immunol. 1995 Oct 15;165(2):183-92. doi: 10.1006/cimm.1995.1204.

Abstract

We have investigated the role of cytokines (IL-2, IL-3, IL-4, IL-6, IFN-gamma, and GM-CSF) in the generation of primary cytotoxic T lymphocytes (CTL), within a single tumor system. The murine carcinoma line 1 was transfected with expression vectors with cDNA for these cytokines. Line 1 expresses low levels of class I MHC molecules, but can be induced with dimethyl sulfoxide or IFN-gamma to express high levels of class I. Class I low line 1 cells are not susceptible to CTL lysis, while class I high line 1 are lysed by CTL, which allows us to assay for CTL activity. To isolate primary CTL, tumor-infiltrating lymphocytes were isolated from cytokine-expressing or control tumors, growing in vivo. Most cytokines stimulated nonspecific killers, but IL-2 and IL-3 stimulated primary CTL. While IFN-gamma alone did not generate primary CTL, coexpression of IFN-gamma with IL-2 resulted in CTL generation. This is the first comparison of the effects of a series of cytokines on primary CTL development, and has important implications for vaccine development and immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Cytokines / physiology*
  • Eosinophils / physiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology
  • Histocompatibility Antigens Class I / analysis
  • Interferon-gamma / physiology
  • Interleukins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • Cytokines
  • Histocompatibility Antigens Class I
  • Interleukins
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor