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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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE88767 | GEO | 2016/10/15

SECONDARY ACCESSION(S): PRJNA348525

REPOSITORIES: GEO

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Project description:Reconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary. C57BL/6 mice were infected intraperitoneally (i.p.) with MCMV strain MW97.01 between 6-16 weeks of age. Splenocytes were isolated from chronically-infected mice and co-stained with three PE-conjugated tetramers loaded with the antigenic peptides from M38, m139 and IE3, all of which promote memory inflation. Cells were then stained with fluorescently conjugated antibodies and sorted on a MoFlo cell sorter. Naïve CD8+ cells were identified as CD44lo. MCMV-specific T cells were identified as CD8+, CD44hi and tetramer binding and then further segregated into memory and effector cells subsets by their expression of KLRG1 and CD127.

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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

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