Abstract
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.
Keywords: Growth Factor, Cancer Research, Natural Killer, Interferon, Small Proportion
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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