Contrary roles of IL-4 and IL-12 on IL-10 production and proliferation of human tumour reactive T cells

Scand J Immunol. 1997 Feb;45(2):221-6. doi: 10.1046/j.1365-3083.1997.d01-386.x.

Abstract

The cytokine profile of tumour reactive T cells is likely to play a central role in their function. However, little is known about how cytokine patterns of tumour reactive T cells can be regulated. Here, the authors investigated the influence of exogenous regulatory cytokines in addition to interleukin-2 (IL-2) on cytokine patterns and the proliferation of T cells recognizing an autologous sarcoma cell line. In this system, IL-4 and IL-12 showed the most polarizing influences on tumour reactive T cells. Exogenous IL-4 induced a predominant production of IL-4 while decreasing the interferon-gamma (IFN-gamma) and IL-10 production by tumour reactive T cells. It also stimulated the growth of tumour reactive CD4+ T cell clones. In contrast, IL-12 substantially increased the production of IL-10 and IFN-gamma. This was accompanied by a growth inhibition of tumour reactive T cells. The growth of CD4+ tumour reactive T cells was also suppressed by exogenous IL-10. This study shows that cytokine patterns and proliferation tumour reactive T cells can be significantly influenced by exogenous cytokines and confirms the hypothesis of a negative feedback loop of IL-12 by the induction of IL-10 in the context of human tumour reactive T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Clone Cells / immunology
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / pharmacology
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / pharmacology*
  • Interleukin-12 / physiology*
  • Interleukin-4 / pharmacology*
  • Interleukin-4 / physiology*
  • Lymphocyte Activation
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Sarcoma / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antigens, CD
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma