Increased Cytotoxic T-cells in the Airways of Adults with Former Bronchopulmonary Dysplasia

Overview

Journal Eur Respir J

Specialty Pulmonary Medicine

Date 2022 Feb 25

PMID 35210327

Authors

Petra Um-Bergstrom

Melvin Pourbazargan

Bettina Brundin

Marika Strom

Monika Ezerskyte

Jing Gao

Eva Berggren Brostrom

Erik Melen

Asa M Wheelock

Anders Linden

C Magnus Skold

Affiliations

Soon will be listed here.

Abstract

Rationale: Bronchopulmonary dysplasia (BPD) in preterm-born infants is a risk factor for chronic airway obstruction in adulthood. Cytotoxic T-cells are implicated in COPD, but their involvement in BPD is not known.

Objectives: To characterise the distribution of airway T-cell subsets in adults with a history of BPD.

Methods: Young adults with former BPD (n=22; median age 19.6 years), age-matched adults born preterm (n=22), patients with allergic asthma born at term (n=22) and healthy control subjects born at term (n=24) underwent bronchoalveolar lavage (BAL). T-cell subsets in BAL were analysed using flow cytometry.

Results: The total number of cells and the differential cell counts in BAL were similar among the study groups. The percentage of CD3CD8 T-cells was higher (p=0.005) and the proportion of CD3CD4 T-cells was reduced (p=0.01) in the BPD group, resulting in a lower CD4/CD8 ratio (p=0.007) compared to the healthy controls (median 2.2 5.3). In BPD and preterm-born study subjects, both CD3CD4 T-cells (r=0.38, p=0.03) and CD4/CD8 ratio (r=0.44, p=0.01) correlated positively with forced expiratory volume in 1 s (FEV). Furthermore, CD3CD8 T-cells were negatively correlated with both FEV and FEV/forced vital capacity (r= -0.44, p=0.09 and r= -0.41, p=0.01, respectively).

Conclusions: Young adults with former BPD have a T-cell subset pattern in the airways resembling features of COPD. Our findings are compatible with the hypothesis that CD3CD8 T-cells are involved in mechanisms behind chronic airway obstruction in these patients.

Citing Articles

Analysis of Predictive Value of Cellular Inflammatory Factors and T Cell Subsets for Disease Recurrence and Prognosis in Patients with Acute Exacerbations of COPD.

Deng H, Zhu S, Yu F, Song X, Jin X, Ding X Int J Chron Obstruct Pulmon Dis. 2024; 19:2361-2369.

PMID: 39502935 PMC: 11537194. DOI: 10.2147/COPD.S490152.

Large airway T cells in adults with former bronchopulmonary dysplasia.

Gao J, Um-Bergstrom P, Pourbazargan M, Berggren-Brostrom E, Li C, Merikallio H Respir Res. 2024; 25(1):86.

PMID: 38336805 PMC: 10858477. DOI: 10.1186/s12931-024-02717-1.

Evolving treatment for prematurity-associated lung disease.

Course C, Kotecha S, Kotecha S Transl Pediatr. 2024; 13(1):1-5.

PMID: 38323186 PMC: 10839272. DOI: 10.21037/tp-23-505.

Evidence of abnormality in glutathione metabolism in the airways of preterm born children with a history of bronchopulmonary dysplasia.

Course C, Lewis P, Kotecha S, Cousins M, Hart K, Heesom K Sci Rep. 2023; 13(1):19465.

PMID: 37945650 PMC: 10636015. DOI: 10.1038/s41598-023-46499-w.

Characterizing the urinary proteome of prematurity-associated lung disease in school-aged children.

Course C, Lewis P, Kotecha S, Cousins M, Hart K, Watkins W Respir Res. 2023; 24(1):191.

PMID: 37474963 PMC: 10357627. DOI: 10.1186/s12931-023-02494-3.

References

Pelkonen A, Suomalainen H, Hallman M, Turpeinen M . Peripheral blood lymphocyte subpopulations in schoolchildren born very preterm. Arch Dis Child Fetal Neonatal Ed. 1999; 81(3):F188-93. PMC: 1721001. DOI: 10.1136/fn.81.3.f188. View

Sutton V, Sedelies K, Dewson G, Christensen M, Bird P, Johnstone R . Granzyme B triggers a prolonged pressure to die in Bcl-2 overexpressing cells, defining a window of opportunity for effective treatment with ABT-737. Cell Death Dis. 2012; 3:e344. PMC: 3406577. DOI: 10.1038/cddis.2012.73. View

Jiang H, Chess L . Regulation of immune responses by T cells. N Engl J Med. 2006; 354(11):1166-76. DOI: 10.1056/NEJMra055446. View

Galderisi A, Calabrese F, Fortarezza F, Abman S, Baraldi E . Airway Histopathology of Adolescent Survivors of Bronchopulmonary Dysplasia. J Pediatr. 2019; 211:215-218. DOI: 10.1016/j.jpeds.2019.04.006. View

Melen E, Guerra S, Hallberg J, Jarvis D, Stanojevic S . Linking COPD epidemiology with pediatric asthma care: Implications for the patient and the physician. Pediatr Allergy Immunol. 2019; 30(6):589-597. DOI: 10.1111/pai.13054. View

Snyder M, Farber D . Human lung tissue resident memory T cells in health and disease. Curr Opin Immunol. 2019; 59:101-108. PMC: 6774897. DOI: 10.1016/j.coi.2019.05.011. View

Kim W, Chi H, Choe K, Oh Y, Lee S, Kim K . A possible role for CD8+ and non-CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema. Respirology. 2013; 18(4):688-96. DOI: 10.1111/resp.12069. View

Caramori G, Casolari P, Barczyk A, Durham A, Di Stefano A, Adcock I . COPD immunopathology. Semin Immunopathol. 2016; 38(4):497-515. PMC: 4897000. DOI: 10.1007/s00281-016-0561-5. View

Robinson P, Latzin P, Verbanck S, Hall G, Horsley A, Gappa M . Consensus statement for inert gas washout measurement using multiple- and single- breath tests. Eur Respir J. 2013; 41(3):507-22. DOI: 10.1183/09031936.00069712. View

10.

Wang Y, Xu J, Meng Y, Adcock I, Yao X . Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018; 13:3341-3348. PMC: 6190811. DOI: 10.2147/COPD.S176122. View

11.

Agusti A, Faner R . Lung function trajectories in health and disease. Lancet Respir Med. 2019; 7(4):358-364. DOI: 10.1016/S2213-2600(18)30529-0. View

12.

Barnes P . Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin Chest Med. 2014; 35(1):71-86. DOI: 10.1016/j.ccm.2013.10.004. View

13.

Hodge S, Hodge G, Holmes M, Jersmann H, Reynolds P . Increased CD8 T-cell granzyme B in COPD is suppressed by treatment with low-dose azithromycin. Respirology. 2014; 20(1):95-100. DOI: 10.1111/resp.12415. View

14.

Kiniwa Y, Miyahara Y, Wang H, Peng W, Peng G, Wheeler T . CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res. 2007; 13(23):6947-58. DOI: 10.1158/1078-0432.CCR-07-0842. View

15.

Walsh M, Wilson-Costello D, Zadell A, Newman N, Fanaroff A . Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol. 2003; 23(6):451-6. DOI: 10.1038/sj.jp.7210963. View

16.

Kinsella J, Greenough A, Abman S . Bronchopulmonary dysplasia. Lancet. 2006; 367(9520):1421-31. DOI: 10.1016/S0140-6736(06)68615-7. View

17.

. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005; 171(8):912-30. DOI: 10.1164/rccm.200406-710ST. View

18.

Bozzetto S, Carraro S, Tomasi L, Berardi M, Zanconato S, Baraldi E . Health-related quality of life in adolescent survivors of bronchopulmonary dysplasia. Respirology. 2016; 21(6):1113-7. DOI: 10.1111/resp.12811. View

19.

Singh R, Alape D, de Lima A, Ascanio J, Majid A, Gangadharan S . Regulatory T Cells in Respiratory Health and Diseases. Pulm Med. 2019; 2019:1907807. PMC: 6886321. DOI: 10.1155/2019/1907807. View

20.

Yang M, Kohler M, Heyder T, Forsslund H, Garberg H, Karimi R . Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respir Res. 2018; 19(1):39. PMC: 5842633. DOI: 10.1186/s12931-017-0699-2. View