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ZAP-70表达与慢性淋巴细胞白血病中CD4中央记忆T细胞增加相关:横断面研究

ZAP-70 expression is associated with increased CD4 central memory T cells in chronic lymphocytic leukemia: cross-sectional study.

作者信息

Correia Rodolfo Patussi, Matos E Silva Flávia Amoroso, Bacal Nydia Strachman, Campregher Paulo Vidal, Hamerschlak Nelson, Amarante-Mendes Gustavo Pessini

机构信息

Instituto Israelita de Ensino e Pesquisa, São Paulo, SP, Brazil.

Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.

出版信息

Hematol Transfus Cell Ther. 2018 Oct-Dec;40(4):317-325. doi: 10.1016/j.htct.2018.03.008. Epub 2018 Jun 11.

Abstract

BACKGROUND

Although chronic lymphocytic leukemia is basically a B cell disease, its pathophysiology and evolution are thought to be significantly influenced by T cells, as these are probably the most important interaction partner of neoplastic B cells, participating in their expansion, differentiation and survival. Chronic lymphocytic leukemia B cells may also drive functional and phenotypic changes of non-malignant T cells. There are few data about the association between memory T cells and prognosis, especially related to ZAP-70, a common reliable surrogate of the gold standard chronic lymphocytic leukemia prognostic markers.

OBJECTIVE

The aim of this study was to investigate whether the expression of ZAP-70 in chronic lymphocytic leukemia patients is associated with abnormal patterns of the distribution of naïve and memory T cells related to crosstalk between these cells.

METHODS

In this cross-sectional, controlled study, patients with chronic lymphocytic leukemia were compared with healthy blood donors regarding the expression of ZAP-70 and the distribution of naïve and memory T cell subsets in peripheral blood as measured by flow cytometry.

RESULTS

ZAP-70 positive patients presented an increased frequency and absolute number of central memory CD4 T cells, but not CD8 T cells, compared to ZAP-70 negative patients and age-matched apparently healthy donors.

CONCLUSIONS

Because central memory CD4 T cells are located in lymph nodes and express CD40L, we consider that malignant ZAP-70-positive B cells may receive beneficial signals from central memory CD4 T cells as they accumulate, which could contribute to more aggressive disease.

摘要

背景

尽管慢性淋巴细胞白血病本质上是一种B细胞疾病,但其病理生理学和演变过程被认为受到T细胞的显著影响,因为T细胞可能是肿瘤性B细胞最重要的相互作用伙伴,参与其扩增、分化和存活。慢性淋巴细胞白血病B细胞也可能驱动非恶性T细胞的功能和表型变化。关于记忆T细胞与预后之间的关联,尤其是与ZAP - 70(一种常见的可靠替代指标,代表金标准慢性淋巴细胞白血病预后标志物)相关的数据很少。

目的

本研究旨在调查慢性淋巴细胞白血病患者中ZAP - 70的表达是否与幼稚和记忆T细胞分布的异常模式相关,这些异常模式与这些细胞之间的相互作用有关。

方法

在这项横断面对照研究中,通过流式细胞术比较慢性淋巴细胞白血病患者与健康献血者外周血中ZAP - 70的表达以及幼稚和记忆T细胞亚群的分布情况。

结果

与ZAP - 70阴性患者及年龄匹配的明显健康献血者相比,ZAP - 70阳性患者的中枢记忆CD4 T细胞频率和绝对数量增加,但CD8 T细胞无此现象。

结论

由于中枢记忆CD4 T细胞位于淋巴结并表达CD40L,我们认为恶性的ZAP - 70阳性B细胞在积累过程中可能从中枢记忆CD4 T细胞接收有益信号,这可能导致疾病更具侵袭性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b25/6200686/dbc4eceaca4b/gr1.jpg

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