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Environmental Health and Preventive Medicine

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Open Access 01-12-2021 | Mesothelioma | Research article

Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction

Authors: Naoko Kumagai-Takei, Yasumitsu Nishimura, Hidenori Matsuzaki, Suni Lee, Kei Yoshitome, Tatsuo Ito, Takemi Otsuki

Published in: Environmental Health and Preventive Medicine | Issue 1/2021

Abstract

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.

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Title: Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction
Authors: Naoko Kumagai-Takei
Yasumitsu Nishimura
Hidenori Matsuzaki
Suni Lee
Kei Yoshitome
Tatsuo Ito
Takemi Otsuki
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Mesothelioma
Published in: Environmental Health and Preventive Medicine / Issue 1/2021
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1186/s12199-021-00967-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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