The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.738056/full |
| _version_ | 1818930231195467776 |
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| author | Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng |
| author_facet | Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng |
| author_sort | Ping-Huai Wang |
| collection | DOAJ |
| description | BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment. |
| first_indexed | 2024-12-20T03:57:24Z |
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| id | doaj.art-e8e45c8f2dd1449597e6ac864c0a948b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T03:57:24Z |
| publishDate | 2021-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-e8e45c8f2dd1449597e6ac864c0a948b2022-12-21T19:54:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.738056738056The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical SeverityPing-Huai Wang0Ming-Fang Wu1Ming-Fang Wu2Chi-Yu Hsu3Sheng-Wei Pan4Sheng-Wei Pan5Chin-Chung Shu6Chin-Chung Shu7Shih-Lung Cheng8Shih-Lung Cheng9Division of Pulmonology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, TaiwanGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Statistical Sciences, Academia Sinica, Taipei, TaiwanCollege of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCollege of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanDivision of Pulmonology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, TaiwanDepartment of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan City, TaiwanBackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2021.738056/fullapoptosiscytokineMycobacterium avium complexnontuberculous mycobacterialung diseaseT-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) |
| spellingShingle | Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity Frontiers in Immunology apoptosis cytokine Mycobacterium avium complex nontuberculous mycobacteria lung disease T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) |
| title | The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity |
| title_full | The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity |
| title_fullStr | The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity |
| title_full_unstemmed | The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity |
| title_short | The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity |
| title_sort | trend of tim3 expression on t cells in patients with nontuberculous mycobacterial lung disease from immune cell dysfunction to clinical severity |
| topic | apoptosis cytokine Mycobacterium avium complex nontuberculous mycobacteria lung disease T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.738056/full |
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