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Immune Signature of Enhanced Functional Avidity CD8+ T Cells in vivo Induced by Vaccinia Vectored Vaccine.

ABSTRACT: Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced in vivo are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8+ T cells with relatively high functional avidity to those from DNA vaccine. Herein, we used functional, immune phenotyping and transcriptomic studies to define the immune signature of these CD8+ T cells with high functional avidity. Antigen-specific CD8+ T cells induced by VACV executed superior in vivo killing activity and displayed a distinct transcriptional profile, whereas no significantly differences were found in composition of memory sub-populations and cytokine poly-functionality. Transcriptional analyses revealed unique features of VACV induced CD8+ T cells in several biological processes, including transport, cell cycle, cell communication and metabolic processes. In summary, we characterize CD8+ T cells of high functional avidity induced in vivo by VACV, which not only improves our understanding of adaptive T cell immunity in VACV vaccination, but also provides clues to modulate functional avidity of CD8+ T cells for T cell based immunotherapy.

SUBMITTER: Hu Z

PROVIDER: S-EPMC5290741 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Immune Signature of Enhanced Functional Avidity CD8<sup>+</sup> T Cells in vivo Induced by Vaccinia Vectored Vaccine.

Hu Zhidong Z Zhu Lingyan L Wang Jing J Wan Yanmin Y Yuan Songhua S Chen Jian J Ding Xiangqing X Qiu Chenli C Zhang Xiaoyan X Qiu Chao C Xu Jianqing J

Scientific reports 20170203

Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced in vivo are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8<sup>+</sup> T cells with relatively high functional avidity to those from DNA vaccine. ...[more]

PMID: 28155878

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Project description:BackgroundBrucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Methodology/principal findingsBlood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-?, and IFN-? in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-?; and HKBM or Rev1-induced secretion of IL-1?, IL-2, GM-CSF, IFN-?, and TNF-?. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1?, IL-2, and TNF-? secretion in response to LPS and HKBM, and IFN-? secretion in response to HKBM.Conclusions/significanceThis work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse.

Dataset Information

Immune Signature of Enhanced Functional Avidity CD8+ T Cells in vivo Induced by Vaccinia Vectored Vaccine.

Publications

Immune Signature of Enhanced Functional Avidity CD8<sup>+</sup> T Cells in vivo Induced by Vaccinia Vectored Vaccine.

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