Correlation of cell‐surface <scp>CD</scp>8 levels with function, phenotype and transcriptome of naive <scp>CD</scp>8 T cells

Balyan, Renu; Gund, Rupali; Chawla, Amanpreet Singh; Khare, Satyajeet P.; Pradhan, Saurabh J.; Rane, Sanket; Galande, Sanjeev; Durdik, Jeannine M.; George, Anna; Bal, Vineeta; Rath, Satyajit

doi:10.1111/imm.13036

Cited by 7 publications

(6 citation statements)

References 41 publications

(64 reference statements)

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“…However, these approaches inevitably depend on the crosstalking between T cells and APCs, as cross-priming of T cells relies on surface markers of APCs 9,10 . Unfortunately, numerous endogenous factors including susceptibility, restricted migration, immune suppression, and metabolic constraints can influence the inherent function of APCs [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross‐Priming of T Cells

Chen

Geng

Wang

et al. 2021

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Despite the activation of T lymphocytes by antigen-presenting cells is responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, we describe the manipulation of cross-priming of T cells using biomimetic nanoparticles (BNs) enabled by cascade cell membrane coating. BNs are resulted from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit intrinsic membrane function of DCs.Strikingly, BNs can directly cross-prime T cells and provoke robust yet antigen-specific antitumor responses in multiple mouse models. Combination with clinical antiprogrammed death-1 antibodies demonstrates a practical way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross-priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy. inoculation with Hepa 1-6 on day 0, the mice were treated with intraperitoneal administration of 100 μg αPD-1 on day 8, 9, 11, 13 and 15 along with daily tail vein injection of HDCNs through day 8 to 14. Equivalent free αPD-1 was used as a control. Mice were sacrificed for sampling once tumor volume in the control group exceeded 2000 mm 3 . Percentages of (a) CD3 + T cells as effector T cells, (b) Ki67 + , (c) IFN-γ + , mean fluorescence intensities of DC indicator (d) CD8 + /Foxp3 + CD25 + CD4 + ratio, (e) CD80 and (f) CD86, and (g) MHC-II in the spleen. Levels of (h) CD3 + CD4 + , (i) IFN-γ and (j) TNF-α in the serum. (k) Average and (l) individual tumor growth curves of the treated mice. Error bars represent the standard deviation (n = 5). Significance was assessed using One-way ANOVA with Dunnett's post-hoc test. ****p < 0.0001, ***p < 0.001 and **p < 0.01.

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Section: Introductionmentioning

confidence: 99%

Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross‐Priming of T Cells

Chen

Geng

Wang

et al. 2021

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“…Interestingly, these two molecules were also co-regulated, such that T cell activation responses were allowed to vary but only within biologically defined limits. Later investigations in naïve T cells expressing high versus low levels of surface CD8 corroborated these findings and demonstrated additional differences in gene expression including cell cycle and pro-apoptotic genes (137). Other experiments sorting naïve cells by glucose uptake capacity or markers of protein synthesis also revealed association with responsiveness to TCR stimulation (53).…”

Section: Origins Of Heterogeneity Among Naïve T Cellsmentioning

confidence: 84%

Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8+ T Cell Responses

Richard

2022

Front. Immunol.

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The advent of technologies that can characterize the phenotypes, functions and fates of individual cells has revealed extensive and often unexpected levels of diversity between cells that are nominally of the same subset. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), are no exception. Investigations of individual CD8+ T cells both in vitro and in vivo have highlighted the heterogeneity of cellular responses at the levels of activation, differentiation and function. This review takes a broad perspective on the topic of heterogeneity, outlining different forms of variation that arise during a CD8+ T cell response. Specific attention is paid to the impact of T cell receptor (TCR) stimulation strength on heterogeneity. In particular, this review endeavors to highlight connections between variation at different cellular stages, presenting known mechanisms and key open questions about how variation between cells can arise and propagate.

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“…The CD8 coreceptor amplifies signals through the TCR ( van den Berg et al, 2007 ; Wooldridge et al, 2010 ). Following antigenic stimulation (e.g., by a virus-infected cell), CD8, along with the TCR, is downregulated from the cell surface, possibly to limit the strength or duration of signaling ( Park et al, 2007 ; Lachmann et al, 2012 ; Balyan et al, 2018 ). This suggests that the expansion of CD8 dim T cells may be a response to high and/or persistent antigen stimulation.…”

Section: Discussionmentioning

confidence: 99%

An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART

Clutton

Weideman

Goonetilleke

et al. 2022

Front. Cell Dev. Biol.

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HIV-associated Kaposi’s sarcoma (KS), which is caused by Kaposi’s sarcoma-associated herpesvirus, usually arises in the context of uncontrolled HIV replication and immunosuppression. However, disease occasionally occurs in individuals with durable HIV viral suppression and CD4 T cell recovery under antiretroviral therapy (ART). The underlying mechanisms associated with this phenomenon are unclear. Suppression of viral infections can be mediated by CD8 T cells, which detect infected cells via their T cell receptor and the CD8 coreceptor. However, CD8 T cells exhibit signs of functional exhaustion in untreated HIV infection that may not be fully reversed under ART. To investigate whether KS under ART was associated with phenotypic and functional perturbations of CD8 T cells, we performed a cross-sectional study comparing HIV-infected individuals with persistent KS under effective ART (HIV+ KS+) to HIV-infected individuals receiving effective ART with no documented history of KS (HIV+ KSneg). A subset of T cells with low cell surface expression of CD8 (“CD8dim T cells”) was expanded in HIV+ KS+ compared with HIV+ KSneg participants. Relative to CD8bright T cells, CD8dim T cells exhibited signs of senescence (CD57) and mitochondrial alterations (PGC-1α, MitoTracker) ex vivo. Mitochondrial activity (MitoTracker) was also reduced in proliferating CD8dim T cells. These findings indicate that an expanded CD8dim T cell population displaying features of senescence and mitochondrial dysfunction is associated with KS disease under ART. CD8 coreceptor down-modulation may be symptomatic of ongoing disease.

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Correlation of cell‐surface CD8 levels with function, phenotype and transcriptome of naive CD8 T cells

Cited by 7 publications

References 41 publications

Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross‐Priming of T Cells

Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross‐Priming of T Cells

Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8+ T Cell Responses

An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART

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