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Production of multiple cytokines by clones of human large granular lymphocytes

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Summary

LGL in addition to mediating natural killer (NK) activity, can secrete a variety of lymphokines, depending on the stimulus used: interleukin-1 (IL-1), interleukin-2 (IL-2), interferon α and γ (IFN), and B-cell growth factor (BCGF). To define more directly whether cells with NK activity can also secrete one or more cytokines, we obtained clones by limiting dilution assays from highly purified preparations of human LGL and cultured them in IL-2-containing medium for several weeks. All the clones tested spontaneously produced detectable levels of IFN-γ and 35 of 40 clones (87%) produced higher levels when stimulated with PHA. A smaller proportion (16%) of clones (9 of 54) secreted IL-1 after stimulation with LPS, while 34% of the clones (17 of 49) produced IL-2 in response to PHA stimulation. Cytokine production was associated with both cytotoxic and noncytotoxic clones and did not correlate with their surface phenotype, as has been observed for fresh LGL. The ability to produce IL-1 or IL-2 was not usually found within the same clones following PHA and LPS stimulation, respectively; however two clones produced both IL-1 and IL-2 when stimulated in different experiments, but not at the same time. In addition, two of nine cloned LGL simultaneously produced IFNγ and IL-1. These results indicate that LGL-derived clones have the ability to produce multiple cytokines, suggesting that the LGL population may play an important immunoregulatory role and may also be capable of self-regulation of cytolytic activity.

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Abbreviations

NK:

natural killer

LGL:

large granular lymphocytes

IL-2:

interleukin 2

IFN:

interferon

IL-1:

interleukin 1

BCGF:

B-cell growth factor

ADCC:

antibody-dependent cellular cytotoxicity

PHA:

phytohemagglutinin A

LPS:

lipopolysaccharide

FBS:

fetal bovine serum

MoAb:

monoclonal antibody

Staph A:

Staphylococcus aureus protein A

FcR:

receptor for the Fc portion of Ig

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Author notes

  1. Paola Allavena

    Present address: Instituto “Mario Negri”, via Eritrea 62, 20157, Milano, Italy

Authors and Affiliations

  1. Biological Therapeutics Branch, National Cancer Institute, 21701, Frederick, MD, USA

    Paola Allavena, Antonio D. Procopio, Ronald B. Herberman & John R. Ortaldo

  2. Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, Frederick Cancer Research Facility, National Cancer Institute, 21701, Frederick, MD, USA

    Giuseppe Scala & Joost J. Oppenheim

  3. Office of Biologics, National Center for Drugs and Biologics, Food and Drug Administration, 20205, Bethesda, MD, USA

    Julie Y. Djeu

Authors
  1. Paola Allavena
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  2. Giuseppe Scala
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  3. Julie Y. Djeu
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  4. Antonio D. Procopio
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  5. Joost J. Oppenheim
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  6. Ronald B. Herberman
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  7. John R. Ortaldo
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Allavena, P., Scala, G., Djeu, J.Y. et al. Production of multiple cytokines by clones of human large granular lymphocytes. Cancer Immunol Immunother 19, 121–126 (1985). https://doi.org/10.1007/BF00199719

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  • DOI: https://doi.org/10.1007/BF00199719

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