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Abstract
Background Interstitial lung abnormalities (ILA) occur in around 10% of subjects over 60 years, and are associated with a higher rate of all-cause mortality. The pathogenic mechanisms are unclear, and the putative contribution of alterations in the immune response has not been explored. Normal ageing is associated with immune deficiencies, including Naïve T-cell decrease and greater expression of the proliferative-limiting, co-inhibitory receptor killer-cell lectin-like receptor G1 (KLRG1).
Objective To evaluate the frequency and activation state of different T-cell subpopulations in ILA subjects.
Methods Peripheral blood mononuclear cells were obtained from 15 individuals with ILA, 21 age-matched controls and 28 healthy young subjects. T-cells phenotype was characterised by flow cytometry, and proliferation and activation by stimulation with anti-CD3/anti-CD28 or phorbol myristate acetate/ionomycin; KLRG1 isoforms were evaluated by western blot and cytokines were quantified by ELISA and Multiplex.
Results A significant increase of Naïve CD4+T cells together with a decrease of central and effector memory CD4+T cells was observed in ILA compared with age-matched controls. CD4+T cells from ILA subjects exhibited greater basal proliferation, which raised after anti-CD3/anti-CD28 stimulation. Additionally, a significant increase in the levels of interleukin-6 and interferon gamma was observed in isolated CD4+T cells and plasma of ILA subjects. They also displayed fewer KLRG1+/CD4+T cells with an increase of circulating E-cadherin, the ligand of KLRG1+. No changes were observed with CD8+T cell subsets.
Conclusion CD4+T cells from ILA subjects are highly proliferative and show an excessive functional activity, likely related to the loss of KLRG1 expression, which may contribute to an inflammatory state and the development of ILA.
- lymphocyte biology
- rare lung diseases
- lung physiology
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Twitter @ChavezGalan78
CM and IB-R contributed equally.
Contributors LC-G and MS conceived and designed the study. CM, RO-G and LC-G performed the experiments. CM, IB-R, LC-G, MM-M, AP and MS examined and interpreted the experimental data. IB-R and MM-M recruited patients and analysed clinical data. CM, IB-R, MM-M and AP contributed to the manuscript preparation. LC-G wrote the manuscript with input from all co-authors. LC-G and MS oversaw all experimental design and manuscript preparation.
Funding This study was supported by Secretaría de Educación, Ciencia, Tecnología e Innovación de la Ciudad de Mexico, grant: SECITI/115/2017 awarded to IB-R; and by CONACYT, grant: FOSISS 290645 awarded to IB-R.
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval Ethics committee/institutional review boards approved the study, protocol numbers: C39-14 and B16-19.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Authors confirm that the raw data to support the conclusions of this study are included in the manuscript. Corresponding author will provide more information, upon rational request, to any qualified researcher.