Increased CD95 (Fas) and PD‐1 expression in peripheral blood T lymphocytes in COVID‐19 patients

Bellesi, Silvia; Metafuni, Elisabetta; Hohaus, Stefan; Maiolo, Elena; Marchionni, Federica; D’Innocenzo, Simone; Sorda, Marilena La; Ferraironi, Manuela; Ramundo, Francesco; Fantoni, Massimo; Murri, Rita; Cingolani, Antonella; Sica, Simona; Gasbarrini, Antonio; Sanguinetti, Maurizio; Chiusolo, Patrizia; Stefano, Valerio De

doi:10.1111/bjh.17034

Cited by 89 publications

(84 citation statements)

References 15 publications

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“…To this end, we observed increased CD25 + T cells in COVID-19 patients, indicating a higher state of activation (Figure 2), but also an increase in CD95 + with disease progression. This phenotype was significantly marked in severe patients, consistent with a recent study 38 . FAS has a crucial role in mediating cell death via FAS ligand engagement, as in activation-induced cell death (AICD), or by shifting cells to a more apoptotic-prone phenotype.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Longitudinal immune profiling of mild and severe COVID-19 reveals innate and adaptive immune dysfunction and provides an early prediction tool for clinical progression

Rendeiro

Casano

Vorkas

et al. 2020

Preprint

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With a rising incidence of COVID-19-associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and adaptive immune cells in disease progression and absolute changes of lymphocyte and myeloid cells in severe versus mild cases or healthy controls. Intubation and death were coupled with selected natural killer cell KIR receptor usage and IgM+ B cells and associated with profound CD4 and CD8 T cell exhaustion. Pseudo-temporal reconstruction of the hierarchy of disease progression revealed dynamic time changes in the global population recapitulating individual patients and the development of an eight-marker classifier of disease severity. Estimating the effect of clinical progression on the immune response and early assessment of disease progression risks may allow implementation of tailored therapies.

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Section: Discussionsupporting

confidence: 92%

“…While previous studies have focused on lymphocyte populations 12,14,15,38 , to our knowledge the role of innate immune cells is less understood 39 . Our study highlights the expansion of MDSCs, especially G-MDSCs, in severe COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal immune profiling of mild and severe COVID-19 reveals innate and adaptive immune dysfunction and provides an early prediction tool for clinical progression

Rendeiro

Casano

Vorkas

et al. 2020

Preprint

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“…T-cell numbers are regulated by proliferation and apoptosis during homeostasis [ 13 ], and accordingly, T-cell reduction in COVID-19 can be due to either or both of increased apoptosis and reduced proliferation rates. While Fas expression is increased in T-cells from COVID-19 [ 14 ], T-cell data in Zhu et al showed that Fas, FasL, and Caspase-3 [ 15 ], which play key roles of T-cell apoptosis, were not significantly increased in COVID-19 patients [ 16 ]. Interleukin (IL)-7 is a key cytokine for T-cell homeostasis, sustaining the naïve T-cell pool [ 17 ].…”

Section: Textmentioning

confidence: 99%

T-cell dysregulation in COVID-19

Kalfaoglu

Almeida‐Santos

Tye

et al. 2021

Biochemical and Biophysical Research Communications

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T-cells play key roles in immunity to COVID-19 as well as the development of severe disease. T-cell immunity to COVID-19 is mediated through differentiated CD4 + T-cells and cytotoxic CD8 + T-cells, although their differentiation is often atypical and ambiguous in COVID-19 and single cell dynamics of key genes need to be characterized. Notably, T-cells are dysregulated in severe COVID-19 patients, although their molecular features are still yet to be fully revealed. Importantly, it is not clear which T-cell activities are beneficial and protective and which ones can contribute to the development of severe COVID-19. In this article, we examine the latest evidence and discuss the key features of T-cell responses in COVID-19, showing how T-cells are dysregulated in severe COVID-19 patients. Particularly, we highlight the impairment of FOXP3 induction in CD4 + T-cells and how the impaired FOXP3 expression can lead to the differentiation of abnormally activated (hyperactivated) T-cells and the dysregulated T-cell responses in severe patients. Furthermore, we characterise the feature of hyperactivated T-cells, showing their potential contribution to T-cell dysregulation and immune-mediated tissue destruction (immunopathology) in COVID-19.

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“…This was accompanied by an increased expression of PD-1 molecules and apoptotic marker, CD95, on T cells and was ascertained regardless of age. The PD-1 levels were positively correlated with CD95 on T cells, indicating the bias of T cells towards exhaustion and apoptosis [152]. This clearly shows that the SARS-CoV-2 virus is intensifying PD-1 protein expression on T cells and driving them to a state of exhaustion and hampering the protective T cell immunity, especially among those who are in a critical condition requiring intensive care unit (ICU) support.…”

Section: Pd-1/pd-l1 Axis During Acute Infections In Blood Vessel Inflmentioning

confidence: 94%

Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance

Veluswamy

Wacker

Scherner

et al. 2020

IJMS

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Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T cell activation by binding to the PD-1 receptor. The general attributes of PD-L1’s immune-suppressive qualities and novel mechanisms on the barrier functions of vascular endothelium to regulate blood vessel-related inflammatory diseases are concisely reviewed. Though targeting the PD-1/PD-L1 axis has received immense recognition—the Nobel Prize in clinical oncology was awarded in the year 2018 for this discovery—the use of therapeutic modulating strategies for the PD-L1/PD-1 pathway in chronic inflammatory blood vessel diseases is still limited to experimental models. However, studies using clinical specimens that support the role of PD-1 and PD-L1 in patients with underlying atherosclerosis are also detailed. Of note, delicate balances in the expression levels of PD-L1 that are needed to preserve T cell immunity and to curtail acute as well as chronic infections in underlying blood vessel diseases are discussed. A significant link exists between altered lipid and glucose metabolism in different cells and the expression of PD-1/PD-L1 molecules, and its possible implications on vascular inflammation are justified. This review summarizes the most recent insights concerning the role of the PD-L1/PD-1 axis in vascular inflammation and, in addition, provides an overview exploring the novel therapeutic approaches and challenges of manipulating these immune checkpoint proteins, PD-1 and PD-L1, for suppressing blood vessel inflammation.

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Increased CD95 (Fas) and PD‐1 expression in peripheral blood T lymphocytes in COVID‐19 patients

Cited by 89 publications

References 15 publications

Longitudinal immune profiling of mild and severe COVID-19 reveals innate and adaptive immune dysfunction and provides an early prediction tool for clinical progression

Longitudinal immune profiling of mild and severe COVID-19 reveals innate and adaptive immune dysfunction and provides an early prediction tool for clinical progression

T-cell dysregulation in COVID-19

Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance

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