Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Kared, Hassen; Tan, Shu Wen; Lau, Mai Chan; Chevrier, Marion; Tan, Crystal Tze Ying; How, Wilson; Wong, Glenn; Strickland, Marie; Malleret, Benoît; Amoah, Amanda; Pilipow, Karolina; Zanon, Veronica; Govern, Naomi Mc; Lum, Josephine; Chen, Jin Miao; Lee, Bernett; Florian, Maria Carolina; Geiger, Hartmut; Ginhoux, Florent; Ruiz‐Mateos, Ezequiel; Fülöp, Tamás; Rajasuriar, Reena; Kamarulzaman, Adeeba; Ng, Tze Pin; Lugli, Enrico; Larbi, Anis

doi:10.1038/s41467-020-14442-6

Cited by 25 publications

(22 citation statements)

References 81 publications

(117 reference statements)

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“…The potential of T SCM to differentiate into various T cell memory subsets might contribute to durable protection against SARS-CoV-2 in COVID-19 convalescent donors. However, Kared et al ., recently showed that an alteration in the Wnt signaling affects the differentiation capabilities of T SCM in older patients 30 .…”

Section: Discussionmentioning

confidence: 99%

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

Kared¹,

Redd

Bloch

et al. 2020

Preprint

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Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

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Section: Discussionmentioning

confidence: 99%

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

Kared¹,

Redd

Bloch

et al. 2020

Preprint

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“…Anis et al found that aging is related to the loss of Wnt/β-catenin signaling in CD4 + TSCM and the increase of Dickkopf-related protein 1 (an inhibitor of the Wnt/β-catenin pathway). This study suggested that targeting Wnt/β could reverse the defect of TSCM through the catenin pathway, which may be a feasible method to restore and maintain immune homeostasis [ 109 ]. These results indicate that it is possible to further optimize culture conditions to obtain T cells with stem cell-like properties more efficiently, thus being able to further maintain and improve cancer immunotherapy.…”

Section: Changes In Senescence-related Immune Cell Subsets In the Tmementioning

confidence: 99%

Immunosenescence: a key player in cancer development

et al. 2020

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Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

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“…Besides the accumulation of senescent T cells, naïve T cells defined by the expression of CD27 and CD45RA have been shown to be dysfunctional with age [73,74]. However, this could be due to the purity of naïve T cells being isolated in those studies as recent studies have demonstrated that naïve T cells remain functional and it is the virtual memory (in mice), human memory T cells with naïve phenotype, and T memory stem cells that are dysfunctional during aging [75][76][77][78][79]. With respect to B cells, an age-associated decline in clonal diversity, the efficiency of the antibody response, and the frequencies of naïve and total B cells in peripheral blood have also been described [80].…”

Section: Senescence Of the Immune Systemmentioning

confidence: 99%

The untwining of immunosenescence and aging

Wong

Hwang

et al. 2020

Semin Immunopathol

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From a holistic point of view, aging results from the cumulative erosion of the various systems. Among these, the immune system is interconnected to the rest as immune cells are present in all organs and recirculate through bloodstream. Immunosenescence is the term used to define the remodelling of immune changes during aging. Because immune cells—and particularly lymphocytes—can further differentiate after their maturation in response to pathogen recognition, it is therefore unclear when senescence is induced in these cells. Additionally, it is also unclear which signals triggers senescence in immune cells (i) aging per se, (ii) specific response to pathogens, (iii) underlying conditions, or (iv) inflammaging. In this review, we will cover the current knowledge and concepts linked to immunosenescence and we focus this review on lymphocytes and T cells, which represent the typical model for replicative senescence. With the evidence presented, we propose to disentangle the senescence of immune cells from chronological aging.

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Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Cited by 25 publications

References 81 publications

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

Immunosenescence: a key player in cancer development

The untwining of immunosenescence and aging

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