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

G. C. Spagnoli, A. Juretic, E. Schultz-Thater, P. Dellabona, L. Filgueira, H. Horig, M. Zuber, G. Garotta, M. Heberer

Research output: Contribution to journalArticle

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-γ, and TNF-α whereas transcription of IL-1-α, 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-γ and TNF-α induced by IL-2, but had no effects on PBMC proliferation and generation of LAK activity. Similarly, purified CD3-/CD16+ lymphocytes, the precursors or 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-γ and TNF-α production but does not affect PBMC proliferation or generation of LAK activity.

Original languageEnglish
Pages (from-to)391-405
Number of pages15
JournalCellular Immunology
Volume146
Issue number2
DOIs
Publication statusPublished - 1993

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Lymphokine-Activated Killer Cells
Interleukin-10
Interleukin-2
Genes
Lymphokines
Blood Cells
Cytokines
Cell Proliferation
Interleukin-3
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Interleukin-4
Interleukin-6
Lymphocytes

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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On the relative roles of interleukin-2 and interleukin-10 in the generation of lymphokine-activated killer cell activity. / Spagnoli, G. C.; Juretic, A.; Schultz-Thater, E.; Dellabona, P.; Filgueira, L.; Horig, H.; Zuber, M.; Garotta, G.; Heberer, M.

In: Cellular Immunology, Vol. 146, No. 2, 1993, p. 391-405.

Research output: Contribution to journalArticle

Spagnoli, GC, Juretic, A, Schultz-Thater, E, Dellabona, P, Filgueira, L, Horig, H, Zuber, M, Garotta, G & Heberer, M 1993, 'On the relative roles of interleukin-2 and interleukin-10 in the generation of lymphokine-activated killer cell activity', Cellular Immunology, vol. 146, no. 2, pp. 391-405. https://doi.org/10.1006/cimm.1993.1035
Spagnoli, G. C. ; Juretic, A. ; Schultz-Thater, E. ; Dellabona, P. ; Filgueira, L. ; Horig, H. ; Zuber, M. ; Garotta, G. ; Heberer, M. / On the relative roles of interleukin-2 and interleukin-10 in the generation of lymphokine-activated killer cell activity. In: Cellular Immunology. 1993 ; Vol. 146, No. 2. pp. 391-405.
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AU - Juretic, A.

AU - Schultz-Thater, E.

AU - Dellabona, P.

AU - Filgueira, L.

AU - Horig, H.

AU - Zuber, M.

AU - Garotta, G.

AU - Heberer, M.

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