# Large airway T cells in adults with former bronchopulmonary dysplasia

**Authors:** Jing Gao, Petra Um-Bergström, Melvin Pourbazargan, Eva Berggren-Broström, ChuanXing Li, Heta Merikallio, Riitta Kaarteenaho, Nichole Stacey Reinke, Craig E Wheelock, Erik Melén, Lindén Anders, Åsa M Wheelock, Georgios Rassidakis, Cristian Ortiz-Villalon, Magnus Carl Sköld

PMC · DOI: 10.1186/s12931-024-02717-1 · Respiratory Research · 2024-02-09

## TL;DR

This study finds that adults born prematurely with BPD have higher levels of cytotoxic T cells in their large airways, which may contribute to chronic airway issues.

## Contribution

The study is the first to characterize T cell profiles in the large airways of adults with former BPD, linking immune cell patterns to lung function.

## Key findings

- Adults with former BPD have significantly higher proportions of lymphocytes and CD8+ T cells in bronchial wash compared to healthy and asthmatic controls.
- CD8+ T cell proportions correlate with lung function metrics like FEV1, suggesting a link between immune profiles and respiratory health.
- The findings suggest that adaptive and innate immune mechanisms may underlie airway disease in those born prematurely with BPD.

## Abstract

Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown.

To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD.

Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry.

The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1.

The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.

The online version contains supplementary material available at 10.1186/s12931-024-02717-1.

Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction in adulthood. Cytotoxic T cells are increased in bronchoalveolar lavage in adults with former BPD.

We are able to demonstrate that inflammatory cell profiles in the bronchial wash from the large airway of preterm adults differ from healthy subjects born at term. Subjects with a history of BPD display an increased proportion of lymphocytes, mainly CD8 + T cells, and a lower proportion of CD4 + T cells. Furthermore, the number of cytotoxic T cells is associated with lung function.

This study provides evidence of an immunological profile characterized by increased cytotoxic T cells in adults born prematurely, which suggests the involvement of both adaptive and innate immune mechanisms in the development of airway disease associated with preterm birth.

The online version contains supplementary material available at 10.1186/s12931-024-02717-1.

## Linked entities

- **Diseases:** Bronchopulmonary Dysplasia (MONDO:0019091), asthma (MONDO:0004979), COPD (MONDO:0005002)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** airway obstruction (MESH:D000402), preterm birth (MESH:D047928), BPD (MESH:D001997), COPD (MESH:D029424), asthma (MESH:D001249)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10858477/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC10858477/full.md

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Source: https://tomesphere.com/paper/PMC10858477