The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency

Our plain-English summary of The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency, by N. Kumagai-Takei, Y. Nishimura, H. Matsuzaki, et al (Journal of Immunology Research, 2016).

The study

• Authors: N. Kumagai-Takei, Y. Nishimura, H. Matsuzaki, S. Lee, K. Yoshitome, H. Hayashi, T. Otsuki
• Journal: Journal of Immunology Research
• Published: 2016;2016:7484872
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We previously reported that exposure to chrysotile B (CB) asbestos suppressed the induction of mature cytotoxic T lymphocytes (CTLs) during mixed lymphocyte reaction assays (MLRs) with a decrease in the proliferation of immature CTLs. However, the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs remains unclear. Since interleukin-2 (IL-2) is a regulator of T lymphocyte proliferation, we examined the effect of IL-2 addition on suppressed CTL differentiation in CB-exposed cultures using flow cytometry (FCM). When IL-2 was added at 1 ng/mL on the second day of MLRs, the asbestos-caused decreases in the proliferation and percentages of CD25+ and CD45RO+ cells in CD8+ lymphocytes were not recovered by IL-2 addition, although the decrease in percentage of granzyme B+ cells was partially recovered. CD8+ lymphocytes from the IL-2-treated culture with asbestos showed the same degree of cytotoxicity as those in cultures without IL-2 or asbestos. These findings indicate that IL-2 insufficiency is not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest a potential for the improvement of such suppressed CTL functions. Secretory factors other than IL-2 in addition to membrane-bound stimulatory molecules may play a role in asbestos-caused suppressed CTL differentiation.

In plain English

This laboratory study used blood cells from healthy volunteers grown in culture; it did not study asbestos-exposed people. The authors had earlier reported that chrysotile B asbestos held back the development of mature killer T cells (cytotoxic T lymphocytes) when cells were stimulated by another person's cells. Here they tested whether a shortage of interleukin-2 (IL-2), a T-cell growth signal, explained this. IL-2 levels did not differ between cultures with and without asbestos. Adding IL-2 on day 2 did not restore the asbestos-related drop in CD8+ T-cell numbers, their multiplication, or their maturation markers. It partly restored the share of CD8+ cells containing granzyme B, a cell-killing protein. Measured as a ratio to cultures without asbestos, that share was 0.5 with asbestos and 0.8 with IL-2 added. CD8+ cells from asbestos cultures given 1 ng/mL IL-2 killed target cells to the same degree as cells from cultures without asbestos or IL-2. The authors concluded that the suppression is not due to IL-2 insufficiency, though IL-2 improved killing ability incompletely. They noted the improved killing may not be specific to the target cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment using mixed lymphocyte reaction assays with human blood cells
• Who was studied: Peripheral blood mononuclear cells (white blood cells) from healthy volunteers, studied at Kawasaki Medical School, Japan. The total number of donors is not stated. The IL-2 measurements used four independent experiments from three individuals.
• Exposure: International Union Against Cancer (UICC) standard chrysotile B asbestos at 5 micrograms per mL in culture. IL-2 at 100 pg/mL or 1 ng/mL was added after 2 days of the assay, for 5 days.
• Main results:
  • IL-2 production did not differ between cultures with and without chrysotile B.
  • Chrysotile B significantly decreased the number of CD3+CD8+ cells, and adding IL-2 did not change either the percentage or the number of these cells in CB-exposed cultures.
  • Adding IL-2 did not restore the asbestos-related changes in the activation and maturation markers CD25, CD45RO and CD45RA in CD8+ lymphocytes.
  • CD8+ lymphocytes purified from asbestos-exposed cultures treated with 1 ng/mL IL-2 showed the same degree of cytotoxicity as those from the control culture without IL-2 or asbestos. These cytotoxicity results are representative data from one of two experiments. Whole blood cells cultured with 100 pg/mL IL-2 showed significantly increased cytotoxicity.
  • The percentage of granzyme B+ cells in CD8+ lymphocytes was measured as a ratio to the allostimulation control. It was significantly lower with chrysotile B (0.5 ± 0.2 ratio, mean ± S.D.). It was partially, but not fully, restored with IL-2 (0.8 ± 0.2 ratio).
  • Adding IL-2 did not restore the asbestos-suppressed proliferation of CD8+ lymphocytes. In asbestos-exposed cultures, granzyme B-positive non-dividing CD8+ cells were 35.2% with IL-2 and 19.3% without IL-2. This difference was a tendency only (p = 0.057).
• The authors' conclusion: The authors concluded that the suppressed induction of cytotoxic T lymphocytes upon asbestos exposure is not attributed to IL-2 insufficiency. They also concluded that adding IL-2 improved the cytotoxicity of asbestos-exposed CD8+ lymphocytes, though incompletely. They suggested that secretory factors other than IL-2, along with membrane-bound stimulatory molecules, might play a role.
• Limitations the authors state:
  • The increased cytotoxicity seen with IL-2 may not be specific against the target cells.
  • The authors have no data explaining why IL-2 did not restore CD8+ lymphocyte proliferation.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Asbestos Exposure.

Related studies

• Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes — N. Kumagai-Takei, Y. Nishimura, et al. (2020)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma — N. Kumagai-Takei, Y. Nishimura, et al. (2014)
• Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers — N. Kumagai-Takei, Y. Nishimura, et al. (2018)
• Safety, feasibility and therapeutic activity of intrapleural autologous lymphocyte conditioned medium followed by systemic recombinant interleukin-2 and interferon-alpha in a patient with malignant pleural mesothelioma — S. Duensing, H. Hamm, et al. (1997)

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