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Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction
Naoko Kumagai-Takei1, Yasumitsu Nishimura2, Hidenori Matsuzaki1,3
1Department of Hygiene, Kawasaki Medical School, Kurashiki, 701-0192, Japan.
Background:
Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8+ T cells. Recently, we reported that asbestos-induced suppression of CTL induction is not due to insufficient levels of interleukin-2 (IL-2). In this study, we continue to investigate the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs and focus on interleukin-15 (IL-15) which is known to be a regulator of T lymphocyte proliferation.
Methods:
For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8+ T cells with fluorescence-labeled anti-CD3, anti-CD8, anti-CD45RA, anti-CD45RO, anti-CD25, and anti-granzyme B antibodies using flow cytometry. To examine the effect of IL-15 on the expression level of intracellular granzyme B in proliferating and non-proliferating CD8+ lymphocytes, PBMCs were stained using carboxyfluorescein diacetate succinimidyl ester (CFSE) and then washed and used for the MLR.
Results:
IL-15 addition partially reversed the decrease in CD3+CD8+ cell numbers and facilitated complete recovery of granzyme B+ cell percentages. IL-15 completely reversed the asbestos-induced decrease in percentage of granzyme B+ cells in both non-proliferating CFSE-positive and proliferating CFSE-negative CD8+ cells. The asbestos-induced decrease in the percentage of CD25+ and CD45RO+ cells in CD8+ lymphocytes was not reversed by IL-15.
Conclusion:
These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.
Insights
Interleukin-15 (IL-15) partially restores antitumor immunity suppressed by asbestos exposure. IL-15 aids in recovering cytotoxic T lymphocyte (CTL) proliferation and function, offering a potential therapeutic avenue against asbestos-induced immune dysfunction.
Area of Science:
- Immunology
- Environmental Health
- Toxicology
Background:
- Asbestos fibers are linked to mesothelioma and suppress antitumor immunity.
- Asbestos exposure reduces cytotoxic T lymphocyte (CTL) induction and CD8+ T cell proliferation.
- Interleukin-2 (IL-2) does not fully explain asbestos-induced CTL suppression.
Purpose of the Study:
- Investigate the role of interleukin-15 (IL-15) in asbestos-induced suppression of CTL differentiation.
- Determine if IL-15 can restore immune function impaired by asbestos exposure.
Main Methods:
- Mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMCs) exposed to chrysotile B asbestos.
- Addition of IL-15 during MLR to assess its impact on CD8+ T cell markers.
- Flow cytometry analysis of T cell proliferation, activation, and cytotoxic markers (e.g., granzyme B).
Main Results:
- IL-15 partially reversed the reduction in CD3+CD8+ T cell numbers caused by asbestos.
- IL-15 fully restored the percentage of granzyme B-positive cells in CD8+ T cells, including both proliferating and non-proliferating populations.
- IL-15 did not reverse the decrease in CD25+ and CD45RO+ cells on CD8+ T lymphocytes.
Conclusions:
- Asbestos-induced CTLs exhibit dysfunction that IL-15 can partially compensate.
- IL-15 is more effective than IL-2 in recovering proliferation and granzyme B levels in asbestos-suppressed CTL induction.
