Age related human T cell subset evolution and senescence

Li, Mingde; Yao, Danlin; Zeng, Xiangbo; Kasakovski, Dimitri; Zhang, Yikai; Chen, Shaohua; Zha, Xianfeng; Li, Yangqiu; Xu, Ling

doi:10.1186/s12979-019-0165-8

Cited by 162 publications

(152 citation statements)

References 26 publications

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“…meaning an increase of T cell memory numbers with frailty, instead of a lower number. It is known that the balance between naïve and memory T cells in peripheral blood changes with advancing age, mainly due to a decline in numbers of naïve (CD8 + ) T cells [11,55,56], which was also observed in our study (data not shown). Only few studies reported relationships between T cell populations and frailty and, to our knowledge, no associations were reported with late differentiated CD4 + TemRA T cells.…”

Section: Discussionsupporting

confidence: 85%

In-depth immune cellular profiling reveals sex-specific associations with frailty

et al. 2020

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Background: With advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether this differs between men and women. Therefore, we performed in-depth immune cellular profiling by enumerating a total of 37 subpopulations of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant's frailty score based on enumeration of immune cell subpopulations. Results: In the association study, frailty was found to be associated with increased numbers of neutrophils in both men and in women. Frailer women, but not men, showed higher numbers of total and CD16monocytes, and lower numbers of both CD56 + T cells and late differentiated CD4 + TemRA cells. The random forest algorithm confirmed all the findings of the association studies in men and women. In men, the predictive accuracy of the algorithm was too low (5.5%) to warrant additional conclusions on top of the ones derived from the association study. In women however, the predictive accuracy was higher (23.1%), additionally revealing that total T cell numbers and total lymphocyte numbers also contribute in predicting frailty. Conclusions: In-depth immune cellular profiling revealed consistent associations of frailty with elevated numbers of myeloid cell subpopulations in both men and women. Furthermore, additional associations were found between frailty and lower numbers of some T cell subpopulations, in women only. Thus, our study indicates sex-specific associations of immune subpopulations with frailty. We hope that our study will prompt further investigation into the sex-specific immune mechanisms associated with the development of frailty.

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Section: Discussionsupporting

confidence: 85%

In-depth immune cellular profiling reveals sex-specific associations with frailty

et al. 2020

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“…We also found reduced expression of the receptor for CXCL9/10/11 (CXCR3), the apoptosis-inducing factor GZMB secreted by NK and T cells, and the effector T-cell marker (CD8A). These data suggest that age-related T-cell and NK cell dysfunction [32,33] may play a role in SARS--CoV-2 pathogenesis in older individuals.…”

Section: Factors Affecting T-cell Trafficking Are Reduced In Older Admentioning

confidence: 73%

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

et al. 2020

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Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCRconfirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly

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“…The odds ratio analysis showed that healthcare workers with current illness were more susceptible to LTBI (OR=3. 39 Table 2)…”

Section: Resultsmentioning

confidence: 99%

“…38 One of the indicators is the changes in the characteristics of the T cells that are very instrumental in resisting attacks from exogenous microorganisms such as viruses and bacteria. 39 This situation will affect increasing susceptibility to various diseases, especially infectious diseases, including TB infections.…”

Section: Discussionmentioning

confidence: 99%

<p>The Prevalence and Demographic Risk Factors for Latent Tuberculosis Infection (LTBI) Among Healthcare Workers in Semarang, Indonesia</p>

Erawati¹,

Andriany²

2020

JMDH

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Purpose: To determine the prevalence and demographic risk factors for latent tuberculosis infection (LTBI) among healthcare workers in Semarang, Indonesia. Methods: A cross-sectional study involving 195 healthcare workers from 34 primary health centers was conducted from August to October 2019. The relationship between independent variables and dependent variables was analyzed using a multivariable logistic regression analysis. Results: The prevalence of LTBI among healthcare workers in this study was 23.6%. Comorbidities were the only risk factor for LTBI identified among other risk factors (OR=3.39, 95% CI: 0.99-11.62, p=0.04). Other demographic factors such as age (OR=0.93, 95% CI: 0.45-1.92, p=0.839), gender (OR=0.79, 95% CI: 0.23-2.72, p=0.708, smoking habits (OR=2.54, 95% CI: 0.52-12.38, p=0.247), and length of work (OR=1.43, 95% CI: 0.70-2.91, p=0.331) were not significant risk factors for LTBI. Conclusion: Healthcare workers suffering from comorbidity have a high risk for tuberculosis infection, and should not work in areas where they would be exposed to patients with tuberculosis. Healthcare workers need to apply occupational safety standards during contact with TB patients or specimens to minimize the disease transmission.

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Age related human T cell subset evolution and senescence

Cited by 162 publications

References 26 publications

In-depth immune cellular profiling reveals sex-specific associations with frailty

In-depth immune cellular profiling reveals sex-specific associations with frailty

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

<p>The Prevalence and Demographic Risk Factors for Latent Tuberculosis Infection (LTBI) Among Healthcare Workers in Semarang, Indonesia</p>

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