On the relative roles of interleukin-2 and interleukin-10 in the generation of lymphokine-activated killer cell activity

Cell Immunol. 1993 Feb;146(2):391-405. doi: 10.1006/cimm.1993.1035.

Abstract

Induction of cytokine gene transcription by recombinant human IL-2 (rhIL-2) in peripheral blood mononuclear cells (PBMC) from healthy donors was studied by qualitative polymerase chain reaction. In all donors tested, optimal doses of rhIL-2-induced transcription of genes encoding for IL-5, GM-CSF, IFN-gamma, and TNF-alpha whereas transcription of IL-1-alpha, IL-3, IL-4, and IL-6 genes could only be detected in about half of the donors. Moreover, we observed that different doses of rhIL-2 were needed to induce transcription of different cytokine genes. In contrast, transcription of IL-2 and IL-10 genes was only observed in a minority of donors, irrespective of the concentration of rhIL-2 used. Since IL-10 displays a well-characterized inhibitory activity on the synthesis of cytokines possibly involved in the generation of lymphokine-activated killer (LAK) cells, we asked whether the absence of IL-10 gene transcription plays a role in the induction of LAK cells. Thus, we tested the effects of different doses of rhIL-10 on the rhIL-2-driven generation of LAK activity. Interestingly, rhIL-10 dose-dependently inhibited the production of IFN-gamma and TNF-alpha induced by IL-2, but had no effects on PBMC proliferation and generation of LAK activity. Similarly, purified CD3-/CD16+ lymphocytes, the precursors of LAK effector cells, could be optimally induced by low doses of rhIL-2 to proliferate and generate MHC-unrestricted cytotoxic activity against NK-resistant targets in the presence of rhIL-10. Altogether, our results indicate that rhIL-2 induces transcription of a preferential pattern of cytokine genes, with the IL-10 gene being infrequently transcribed. On the other hand, rhIL-10 shows diverse effects on rhIL-2-triggered PBMC activation, in that it inhibits IFN-gamma and TNF-alpha production but does not affect PBMC proliferation or generation of LAK activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cytokines / genetics
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Interleukin-2 / pharmacology*
  • Killer Cells, Lymphokine-Activated / drug effects*
  • Killer Cells, Lymphokine-Activated / immunology
  • Leukocytes, Mononuclear / immunology*
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic / drug effects

Substances

  • Cytokines
  • Interleukin-2
  • Recombinant Proteins
  • Interleukin-10