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Open Access 01-12-2022 | Smoking and Nicotine Detoxification | Research

Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults

Authors: Juliana Ruiz Fernandes, Thalyta Nery Carvalho Pinto, Liã Barbara Arruda, Cibele Cristine Berto Marques da Silva, Celso Ricardo Fernandes de Carvalho, Regina Maria Carvalho Pinto, Alberto José da Silva Duarte, Gil Benard

Published in: Immunity & Ageing | Issue 1/2022

Abstract

Background

COPD is associated with an abnormal lung immune response that leads to tissue damage and remodeling of the lung, but also to systemic effects that compromise immune responses. Cigarette smoking also impacts on innate and adaptative immune responses, exerting dual, pro- and anti-inflammatory effects. Previously, we showed that COPD patients presented accelerated telomere shortening and decreased telomerase activity, while, paradoxically, cigarette-smokers exhibited preserved telomerase activity and slower rate of telomere shortening.

Results

Here, we evaluated the naive, CM, EM and T^EMRA subsets of TCD4 and TCD8 cells according to the expression of CCR7/CD45RA. We compared age-matched COPD patients, cigarette-smokers without clinical-laboratory evidence of pulmonary compromise, and healthy individuals. They were additionally compared with a group of young adults. For each subset we analysed the expression of markers associated with late differentiation, senescence and exhaustion (CD27/CD28/CD57/KLRG1/PD1). We show that COPD patients presented a drastically reduced naive cells pool, and, paradoxically, increased fractions of naive cells expressing late differentiation, senescence or exhaustion markers, likely impacting on their immunocompetence. Pronounced phenotypic alterations were also evidenced in their three memory T-cell subsets compared with the other aged and young groups, suggesting an also dysfunctional memory pool. Surprisingly, our smokers showed a profile closer to the Healthy aged than COPD patients. They exhibited the usual age-associated shift of naive to EM TCD4 and TCD8 cells, but not to CM or T^EMRA T-cells. Nonetheless, their naive T-cells phenotypes were in general similar to those of the Youngs and Healthy aged, suggesting a rather phenotypically preserved subset, while the memory T-cells exhibited increased proportions of cells with the late-differentiation or senescence/exhaustion markers as in the Healthy aged.

Conclusion

Our study extends previous findings by showing that COPD patients have cells expressing a full range of late differentiated, senescent or exhausted phenotypes encompassing all TCD4 and TCD8 subsets, consistent with a premature immunosenescence phenotype. Surprisingly, the smokers group’s results suggest that moderate to heavy chronic cigarette smoking did not accelerate the pace of immunosenescence as compared with the Healthy aged.

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Title: Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults
Authors: Juliana Ruiz Fernandes
Thalyta Nery Carvalho Pinto
Liã Barbara Arruda
Cibele Cristine Berto Marques da Silva
Celso Ricardo Fernandes de Carvalho
Regina Maria Carvalho Pinto
Alberto José da Silva Duarte
Gil Benard
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Smoking and Nicotine Detoxification
Chronic Obstructive Lung Disease
Published in: Immunity & Ageing / Issue 1/2022
Electronic ISSN: 1742-4933
DOI: https://doi.org/10.1186/s12979-022-00267-y

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