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Published on: January 15, 2011
Interleukin 15 is a potent stimulant of intraepithelial lymphocytes
1Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Insights
Interleukin-15 (IL-15) significantly enhances intraepithelial lymphocyte (IEL) proliferation, interferon-gamma production, and cytotoxicity, making it a potent cytokine for IEL activation.
Area of Science:
- Immunology
- Cell Biology
- Gastrointestinal Research
Background:
- Intraepithelial lymphocytes (IELs) resemble memory cells and are positioned adjacent to IL-15-producing epithelial cells.
- The role of IL-15 in IEL function warrants investigation due to this proximity and cellular resemblance.
Purpose of the Study:
- To investigate the effects of interleukin-15 (IL-15) on the functional properties of intraepithelial lymphocytes (IELs).
- To compare the potency of IL-15 with other cytokines like IL-2 and IL-7 in stimulating IEL responses.
Main Methods:
- [3H]thymidine uptake was used to measure IEL proliferation.
- Enzyme-linked immunosorbent assay (ELISA) quantified interferon-gamma (IFN-gamma) production.
- Cytotoxicity was assessed by the lysis of 51Cr-labeled HT-29 cells and limiting dilution analysis for cytotoxic precursors.
Main Results:
- IL-15 induced significantly greater IEL proliferation and blastogenesis compared to IL-2 and IL-7.
- IL-15 stimulation resulted in the highest production of IFN-gamma by IELs.
- IELs cultured with IL-15 exhibited enhanced cytotoxicity against HT-29 cells and a greater frequency of cytotoxic precursors than those with IL-2.
Conclusions:
- Interleukin-15 (IL-15) is identified as the most potent cytokine for stimulating intraepithelial lymphocytes (IELs).
- IL-15 effectively drives IEL proliferation, IFN-gamma production, and cytotoxic activity.
- The findings highlight IL-15's crucial role in IEL-mediated immune responses.
Background & Aims:
This study examined the effects of interleukin (IL)-15 on intraepithelial lymphocytes (IELs) because they resemble memory cells that react to IL-15 and are located next to epithelial cells that produce IL-15.
Methods:
Proliferative responses were measured by [3H]thymidine uptake; interferon (IFN)-gamma production by enzyme-linked immunosorbent assay; and cytotoxicity production by lysis of 51Cr-labeled HT-29 cells.
Results:
The proliferative response of IELs was much greater with IL-15 than with equivalent amounts of IL-2 or IL-7 (P < 0.001); the same level of blastogenesis was induced by 10(3)-fold less IL-15 than IL-2. Production of IFN-gamma was also highest when IELs were stimulated with IL-15. IELs lysed more 51Cr-labeled HT-29 cells when cultured for 72 hours with IL-15 (48% +/- 3% at 25:1 effector-to-target ratio) than with IL-2 (27% +/- 3%) or IL-7 (12% +/- 2%) (P < 0.0001). Similarly, limiting dilution analysis revealed a greater frequency of cytotoxic precursors in IELs that were stimulated by IL-15 rather than IL-2: 1/467 vs. 1/1900. But IL-15 did not alter the number of natural killer cells, as determined by quantitating CD16 and CD56 by immunofluorescence. Rather, it increased serine esterase content in IELs.
Conclusions:
IL-15 is the most potent of the known cytokines for IELs, inducing the highest levels of proliferation, IFN-gamma production, and cytotoxicity.
