Accumulation of CD28null Senescent T-Cells Is Associated with Poorer Outcomes in COVID19 Patients

Coleman, Mia J.; Zimmerly, Kourtney M.; Yang, Xuexian O.

doi:10.3390/biom11101425

Cited by 14 publications

(11 citation statements)

References 156 publications

(250 reference statements)

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“…Senescent CD8 + T-cell population increase in aged people, in younger individuals with chronic viral infections, and in patients with certain types of cancers [124,131]. Moreover, Treg cells (natural Tregs or nTregs, and tumour-derived Tregs), as well as tumour cells, suppress the function of na€ ıve and effector T cells by inducing T-cell senescence [126,132,133,134].…”

Section: Immunosenescence Is Associated With Impaired Anti-tumour Imm...mentioning

confidence: 99%

Cellular senescence and the tumour microenvironment

2022

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The senescence‐associated secretory phenotype (SASP), where senescent cells produce a variety of secreted proteins including inflammatory cytokines, chemokines, matrix remodelling factors, growth factors and so on, plays pivotal but varying roles in the tumour microenvironment. The effects of SASP on the surrounding microenvironment depend on the cell type and process of cellular senescence induction, which is often associated with innate immunity. Via SASP‐mediated paracrine effects, senescent cells can remodel the surrounding tissues by modulating the character of adjacent cells, such as stromal, immune cells, as well as cancer cells. The SASP is associated with both tumour‐suppressive and tumour‐promoting effects, as observed in senescence surveillance effects (tumour‐suppressive) and suppression of anti‐tumour immunity in most senescent cancer‐associated fibroblasts and senescent T cells (tumour‐promoting). In this review, we discuss the features and roles of senescent cells in tumour microenvironment with emphasis on their context‐dependency that determines whether they promote or suppress cancer development. Potential usage of recently developed drugs that suppress the SASP (senomorphics) or selectively kill senescence cells (senolytics) in cancer therapy are also discussed.

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Section: Immunosenescence Is Associated With Impaired Anti-tumour Imm...mentioning

confidence: 99%

Cellular senescence and the tumour microenvironment

2022

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“…We also discovered that the percentage of CD4 + CD28-T cells was significantly lower in the group treated with 300 mg of MLE compared to the positive controls. − T cells resistance of CD28 − T cells depends on a decrease in the pro-apoptotic molecule, Fas, Bim, and Bax, or an increase in the anti-apoptotic molecule Bcl2 [30]. The mango's mistletoe leaf extract (MLE) can reduce the percentage of CD28 − presumably by increasing the BAX/BCL2 ratio and BAK expression [22], [31].…”

Section: Cd28mentioning

confidence: 99%

“…The mango's mistletoe leaf extract (MLE) can reduce the percentage of CD28 − presumably by increasing the BAX/BCL2 ratio and BAK expression [22], [31]. In addition, MLE presumably decreases TNF-α which interferences CD28 expression on T cells [22], inhibits IL-15 and IL-6 that promote the development and maintenance of CD28 − T cells [30], [32], and inhibits P38, ERK1/2, and STAT 3 which play a role in immunosenescence [22], [33], [34]. This result is in line with that of the previous research that quercetin treatment of murine DCs resulted in a decrease in…”

Section: Cd28mentioning

confidence: 99%

The Mango’s Mistletoe Leaves Extract Ameliorates Lupus by Inhibiting the Anti-dsDNA Antibody Production, the Percentages of CD8+CD28− and CD4+CD28− T Cells

Handono¹,

Sunarti²,

Pratama³

et al. 2022

Open Access Maced J Med Sci

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BACKGROUND: In SLE patients, repeated antigen stimulations induce a progressive reduction in CD28 expression on the surface of T cells and the chronic inflammation condition. Mango’s mistletoe is a parasitic plant that has anti-inflammation, antiproliferation, and immunomodulatory activities. AIM: This study aimed to investigate the effect of mango’s mistletoe leaves extract (MLE) in inhibiting anti-dsDNA antibodies and ameliorating the percentages of CD8+CD28− and CD4+CD28− T cells in a pristane-induced lupus mice model. METHODS: Lupus induction was undertaken by an injection of pristane 0.5 ml intraperitoneally in 6–8-week-old female balb/c mice. Mice with lupus signs were grouped randomly into the treatment groups which received MLE at doses of 150, 300, and 600 mg/kgbw/d for 28 days, respectively, and the positive control group without MLE. On day 29, anti-dsDNA antibody levels were analyzed using an ELISA. One of the immunosenescence markers (CD28− T cells) was investigated using a flow cytometer. ANOVA test was used for statistical analysis. RESULTS: The mango’s mistletoe leaves extract (MLE) significantly decreased the number of anti-dsDNA antibodies (*p < 0.05), the percentages of CD8+CD28− T cells (*p < 0.05) and CD4+CD28− T cells (*p < 0.05). CONCLUSION: We resume that the mango’s mistletoe leaves can ameliorate lupus by inhibiting anti-dsDNA antibody production and the percentages of CD8+CD28− and CD4+CD28− T cells.

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“…Age-associated dysfunction of the immune system, referred to as immunosenescence, renders older adults more susceptible to infection by emerging viruses and less responsive to vaccination, which can be partly explained by a decline in T cell immunity ( 15 ). This age-related immune dysfunction has also been associated with persistent latent infections, as caused by cytomegalovirus (CMV), of which the hallmark is to induce immunosenescent CD28 - T cells that have been previously linked to increased risk of COVID-19 severity and hospitalization ( 16 , 17 ). CMV incidence in the Netherlands ranges from 45% in younger adults to nearly 80% in the population >80 years old ( 18 , 19 ), thus being a potential factor contributing to impaired T cell immunity against COVID-19 among older adults.…”

Section: Introductionmentioning

confidence: 99%

Distinct T cell responsiveness to different COVID-19 vaccines and cross-reactivity to SARS-CoV-2 variants with age and CMV status

Brummelman,

Suárez-Hernández,

de Rond

et al. 2024

Front. Immunol.

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IntroductionAccumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs.MethodsTherefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs.ResultsRobust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination.DiscussionTogether, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.

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Accumulation of CD28null Senescent T-Cells Is Associated with Poorer Outcomes in COVID19 Patients

Cited by 14 publications

References 156 publications

Cellular senescence and the tumour microenvironment

Cellular senescence and the tumour microenvironment

The Mango’s Mistletoe Leaves Extract Ameliorates Lupus by Inhibiting the Anti-dsDNA Antibody Production, the Percentages of CD8+CD28− and CD4+CD28− T Cells

Distinct T cell responsiveness to different COVID-19 vaccines and cross-reactivity to SARS-CoV-2 variants with age and CMV status

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