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Expression data from CD28+/- resting CD8 T cells

ABSTRACT: Expression data from CD28+/- resting CD8 T cells

PROVIDER: PRJNA414963 | ENA |

REPOSITORIES: ENA

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Expression data from CD28+/- resting CD8 T cells

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Differentiated expression profiling between CD8+CD28+ T cell subset and CD8+CD28- T cell subset using long non coding RNA microarray in five healthy Chinese nonagenarians

Project description:To obtain the differentiated profiling of long noncoding RNA expression between CD8+CD28+ T cell subset and CD8+CD28- T cell subset, we have detecte lncRNA profiling between within-individual T cell subsets to identify differentiated lncRNA profiling in five apperant healthy Chinese nenogenarians who were cytomegalovirus-seropositive carriers. Human peripheral blood monocytes from these apperantly healthy CMV-seropositive nonagenarians was gathered. CD8+CD28+ T cells and CD8+CD28- T cells were further isolated using flow cytometry. Differentiated lncRNA profiling was compared between CD8+CD28+ T cells and CD8+CD28- T cells using lncRNA microarry detection within-individually. 586 lncRNAs were found significantly upregulated while 1113 lncRNAs were found significantly downregulated comparing CD8+CD28+ T cells with CD8+CD28- T cells in these Chinese nonagenarians with CMV seropositivity. Expression of ENST00000446590,NR_121652,NR_045006,ENST00000428936,NR_110375 from this differentiated profiling which were identified as previously domumented ageing-related lncRNAs were quantified in the same RNA samples by real-time PCR, confirming lncRNAs take critical role in regulating T cell immunosenesence in healthy nonagenarian Chinese CMV carriers. Diffentiated lncRNA profiling was in-pair compared between total RNAs isolated from CD8+CD28+ T cells and CD8+CD28- T cells within-individually in Chinese nonagenarian CMV carriers.

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PD-1 blockade-unresponsive human tumor-infiltrating CD8+ T cells are marked by loss of CD28 expression and rescued by IL-15

Project description:Blockade of programmed death-1 (PD-1) reinvigorates exhausted CD8+ T cells, resulting in tumor regression in cancer patients. Recently, reinvigoration of exhausted CD8+ T cells following PD-1 blockade was shown to be CD28-dependent in mouse models. Herein, we examined the role of CD28 in anti-PD-1-induced human T-cell reinvigoration using tumor-infiltrating CD8+ T cells (CD8+ TILs) obtained from non-small cell lung cancer patients. Single cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8+ TILs. Furthermore, we found that human CD28+CD8+, but not CD28–CD8+ TILs, responded to PD-1 blockade irrespective of B7/CD28 blockade, indicating that CD28 co-stimulation in human CD8+ TILs is dispensable for PD-1 blockade-induced reinvigoration, and loss of CD28 expression rather serve as a marker of anti-PD-1-unresponsive CD8+ TILs. Transcriptionally and phenotypically, PD-1 blockade-unresponsive human CD28–PD-1+CD8+ TILs exhibited characteristics of terminally exhausted CD8+ T cells with low TCF1 expression. Notably, CD28–PD-1+CD8+ TILs had preserved machinery to respond to IL-15, and IL-15 treatment enhanced proliferation of CD28–PD-1+CD8+ TILs as well as CD28+PD-1+CD8+ TILs. Taken together, we demonstrate loss of CD28 expression as a marker of PD-1 blockade-unresponsive human CD8+ TILs with TCF1– signature and provide mechanistic insights into combining IL-15 with anti-PD-1.

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