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真性红细胞增多症患者中独特的 CD8 T 细胞和 MHC Ⅰ类分子特征。

Distinctive CD8 T cell and MHC class I signatures in polycythemia vera patients.

机构信息

CICS-UBI-Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal.

FCS-Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.

出版信息

Ann Hematol. 2018 Sep;97(9):1563-1575. doi: 10.1007/s00277-018-3332-7. Epub 2018 May 22.

DOI:10.1007/s00277-018-3332-7
PMID:29789880
Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as βm-associated and βm-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3CD8 T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3CD8 T cell population enriched in effector-memory CD45RA T cells (CD8 TEMRA) when compared to CTR (P < 0.001), and a less granular CD3CD8 T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8 T) and CD8 TEMRA cells expressing intermediate levels of CD28, i.e., CD3CD8CD28. While the percentage of CD3CD8 TN cells correlated positively with the number of erythrocytes, the percentage of CD3CD8 TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10) MHC-I conformers. The implications of this distinctive immune signature are discussed.

摘要

真性红细胞增多症(PV)是一种骨髓增生性肿瘤,其特征是红细胞过度生成。我们对 PV 患者和年龄匹配的对照组(CTR)的血液免疫细胞进行了全面的特征分析,以研究其幼稚和记忆受体以及βm 相关和βm 游离 MHC Ⅰ类重链(分别称为封闭和开放构象)的表达。结果表明,与 CTR 相比,PV 患者外周血 CD3CD8 T 细胞群明显分为两个离散的群体,即效应记忆 CD45RA T 细胞(CD8 TEMRA)更为丰富的更具颗粒性的 CD3CD8 T 细胞群体(P<0.001),以及在 CTR 组中完全不存在的较少颗粒性的 CD3CD8 T 细胞群体(78%比 0%,P<0.001),并且是表达中间水平 CD28 的幼稚(CD8 T)和 CD8 TEMRA 细胞的混合物,即 CD3CD8CD28。虽然 CD3CD8 TN 细胞的百分比与红细胞数量呈正相关,但是 CD3CD8 TEMRA 的百分比与血小板数量呈负相关。最后,我们报告称,PV 患者的淋巴细胞和单核细胞表面的封闭(W6/32)MHC-I 构象体水平较低,而开放(HC-10)MHC-I 构象体水平较高。讨论了这种独特免疫特征的意义。

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