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一种用于分析过继转移T细胞的安全性、持久性和功能的非人灵长类动物模型。

A non-human primate model for analysis of safety, persistence, and function of adoptively transferred T cells.

作者信息

Berger C, Berger M, Anderson D, Riddell S R

机构信息

Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

出版信息

J Med Primatol. 2011 Apr;40(2):88-103. doi: 10.1111/j.1600-0684.2010.00451.x. Epub 2010 Nov 2.

DOI:10.1111/j.1600-0684.2010.00451.x
PMID:21044089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3048898/
Abstract

BACKGROUND

Adoptive immunotherapy with antigen-specific effector T-cell (T(E) ) clones is often limited by poor survival of the transferred cells. We describe here a Macaca nemestrina model for studying transfer of T-cell immunity.

METHODS

We derived, expanded, and genetically marked CMV-specific CD8(+) T(E) clones with surface markers expressed on B cells. T(E) cells were adoptively transferred, and toxicity, persistence, retention of introduced cell-surface markers, and phenotype of the persisting T cells were evaluated.

RESULTS

CD8(+) T(E) clones were efficiently isolated from distinct memory precursors and gene-marking with CD19 or CD20 permitted in vivo tracking by quantitative PCR. CD19 was a more stable surface marker for tracking cells in vivo and was used to re-isolate cells for functional analysis. Clonally derived CD8(+) T(E) cells differentiated in vivo to phenotypically and functionally heterogeneous memory T-cell subsets.

CONCLUSIONS

These studies demonstrate the utility of Macaca nemestrina for establishing principles for T-cell therapeutics applicable to humans.

摘要

背景

采用抗原特异性效应T细胞(T(E))克隆进行过继性免疫治疗常常受到转移细胞存活率低的限制。我们在此描述一种用于研究T细胞免疫转移的豚尾猕猴模型。

方法

我们获得、扩增并对具有B细胞表面标志物的巨细胞病毒特异性CD8(+) T(E)克隆进行基因标记。过继性转移T(E)细胞,并评估毒性、持久性、引入的细胞表面标志物的保留情况以及持久性T细胞的表型。

结果

从不同的记忆前体中有效分离出CD8(+) T(E)克隆,用CD19或CD20进行基因标记可通过定量PCR在体内追踪。CD19是体内追踪细胞更稳定的表面标志物,用于重新分离细胞进行功能分析。克隆衍生的CD8(+) T(E)细胞在体内分化为表型和功能异质性的记忆T细胞亚群。

结论

这些研究证明了豚尾猕猴在确立适用于人类的T细胞疗法原则方面的实用性。

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