ge-associated phenotypic imbalance in TCD4 and TCD... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Fernandes, Juliana Ruiz [1] ; Carvalho Pinto, Thalyta Nery [1] ; Arruda, Lia Barbara [2] ; Berto Marques da Silva, Cibele Cristine [3] ; Fernandes de Carvalho, Celso Ricardo [3] ; Carvalho Pinto, Regina Maria [4] ; da Silva Duarte, Alberto Jose [1] ; Benard, Gil [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Sch Med, Trop Med Inst, Lab Dermatol & Immunodeficiencies LIM56, Av Dr Arnaldo 455, Sao Paulo - Brazil
[2] UCL, Ctr Clin Microbiol, Div Infect & Immun, Royal Free Hosp Campus, London - England
[3] Univ Sao Paulo, Sch Med, Dept Phys Therapy, R Dr Ovidio Pires de Campos 255, Sao Paulo - Brazil
[4] Univ Sao Paulo, Sch Med, Heart Inst InCor, Pulm Dept, Av Dr Eneas de Carvalho Aguiar 44, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: IMMUNITY & AGEING; v. 19, n. 1 FEB 14 2022.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 18/06063-8 - Immunosenescence on Chronic Obstructive Pulmonary Disease
Grantee:Gil Benard
Support Opportunities: Regular Research Grants