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Killer-cell inhibitory receptors, CD158a/b, are upregulated by interleukin-2, but not interferon-gamma or
T Kogure1, H Fujinaga, A Niizawa
1Department of Japanese Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University. kogu2737@ms.toyama-mpu.ac.jp
Abstract:
Although it is now accepted that killer-cell inhibitory receptors (KIRs), which were molecularly cloned in 1995, deliver negative signals to natural killer (NK) cells regarding the recognition of target cells, it is still unclear how the expression of these receptors on lymphocytes is regulated. Therefore, we investigated the regulation of expression of representative KIRs, CD158a and CD158b, by cytokines such as interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma). Neither IL-4 nor IFN-gamma affected the expression of CD158a/b, but incubation for 48 h with IL-2, which enhances the killer activity of NK cells, upregulated the expression of the KIRs. This upregulation by IL-2 was also observed in CD16-positive cells sorted from total lymphocytes. In contrast, IL-4, which is a down-regulator of IL-2-induced killer responses, did not change the level of CD158a/b expression when added after the IL-2 treatment. These findings suggest that IL-2 plays an important role in the regulation of CD158a/b expression, and might be involved in controlling NK activity via regulating expression of these molecules.
Insights
Interleukin-2 (IL-2) upregulates killer-cell inhibitory receptors (KIRs) on natural killer (NK) cells. This IL-2 effect on KIR expression may control NK cell activity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Killer-cell inhibitory receptors (KIRs) mediate negative signals to natural killer (NK) cells.
- The regulation of KIR expression on lymphocytes remains largely unknown.
Purpose of the Study:
- To investigate the regulation of CD158a and CD158b (KIRs) expression by cytokines.
- To determine the role of IL-2, IL-4, and IFN-gamma in KIR expression.
Main Methods:
- Incubation of lymphocytes with IL-2, IL-4, and IFN-gamma.
- Analysis of CD158a/b expression levels.
- Sorting of CD16-positive cells for further analysis.
Main Results:
- IL-2 upregulated CD158a/b expression on NK cells after 48 hours.
- IL-4 and IFN-gamma did not affect CD158a/b expression.
- IL-2-induced upregulation of KIRs was confirmed in CD16-positive cells.
Conclusions:
- IL-2 plays a significant role in regulating CD158a/b expression.
- IL-2 may control NK cell activity by modulating KIR expression.