Journal Article

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

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

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aging / Antibodies / Antigens / Biomedical and Life Sciences / Biomedicine / CCR7 protein / CD27 antigen / CD28 antigen / CD45RA antigen / CD57 antigen / Cell cycle / Cell differentiation / Cellular senescence / Chronic illnesses / Chronic obstructive pulmonary disease / Cigarette smoke / Cigarette smoking / Cigarettes / Clinical Nutrition / Comparative analysis / COPD / Cytokines / Cytotoxicity / Disease susceptibility / Evaluation / Genotype & phenotype / Geriatrics/Gerontology / Immune response / Immune system / Immunocompetence / Immunological memory / Immunology / Immunophenotyping / Immunosenescence / Infections / Inflammation / KLRG1 protein / Ligands / Lung diseases / Lung diseases, Obstructive / Lymphocytes / Lymphocytes T / Medical research / Medicine, Experimental / Memory cells / Patients / PD-1 protein / Phenotypes / Public Health / Senescence / Smokers / Smoking / Smoking and youth / T cells / Teenagers / Telomerase / Telomeres / Young adults / Youth