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巴西里约热内卢州皮肤利什曼病患者CD8 + T淋巴细胞亚群的T细胞受体Vβ谱

T-cell receptor Vβ repertoire of CD8+ T-lymphocyte subpopulations in cutaneous leishmaniasis patients from the state of Rio de Janeiro, Brazil.

作者信息

Ferraz Raquel, Cunha Clarissa Ferreira, Pimentel Maria Inês, Lyra Marcelo Rosandiski, Schubach Armando Oliveira, Mendonça Sérgio Coutinho Furtado de, Da-Cruz Alda Maria, Bertho Alvaro Luiz

机构信息

Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.

Laboratório de Vigilância em Leishmaniose, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.

出版信息

Mem Inst Oswaldo Cruz. 2015 Aug;110(5):596-605. doi: 10.1590/0074-02760150039. Epub 2015 Jun 24.


DOI:10.1590/0074-02760150039
PMID:26107186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4569821/
Abstract

In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+T-cells are associated with larger lesions.

摘要

在人类皮肤利什曼病(CL)中,免疫反应主要由T细胞介导。与愈合或有害功能相关的CD8 + T淋巴细胞在影响临床结局中的作用存在争议。本研究的目的是评估晚期分化效应(LDE)和记忆CD8 + T细胞亚群中的T细胞受体多样性,以便创建参与有害或保护性CL免疫反应的特定克隆图谱。健康受试者、活动性疾病患者(PAD)和临床治愈患者被纳入该研究。总CD8 + T淋巴细胞在Vβ2、Vβ9、Vβ13.2、Vβ18和Vβ23家族的表达上出现紊乱。对CD8 + T淋巴细胞亚群的分析显示,PAD中表达Vβ12和Vβ22的LDE CD8 + T淋巴细胞频率较高,以及表达Vβ22的效应记忆CD8 + T细胞频率较高。我们还观察到PAD中表达Vβ2的效应和中枢记忆CD8 + T细胞频率较低,这与更大的病变大小相关。特定的Vβ扩增指向CL免疫反应期间被选择的CD8 + T细胞克隆,表明表达Vβ12或Vβ22的CD8 + T淋巴细胞参与LDE反应,并且记忆CD8 + T细胞中的Vβ2收缩与更大的病变相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/257637e16828/0074-0276-mioc-110-5-0596-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/7edb496c0a25/0074-0276-mioc-110-5-0596-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/4c8e8dba0010/0074-0276-mioc-110-5-0596-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/ae9e8b3e760c/0074-0276-mioc-110-5-0596-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/20db59bf599b/0074-0276-mioc-110-5-0596-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/257637e16828/0074-0276-mioc-110-5-0596-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/7edb496c0a25/0074-0276-mioc-110-5-0596-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/4c8e8dba0010/0074-0276-mioc-110-5-0596-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/ae9e8b3e760c/0074-0276-mioc-110-5-0596-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/20db59bf599b/0074-0276-mioc-110-5-0596-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dac/4569821/257637e16828/0074-0276-mioc-110-5-0596-gf05.jpg

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本文引用的文献

[1]
Apoptosis and frequency of total and effector CD8+ T lymphocytes from cutaneous leishmaniasis patients during antimonial therapy.

BMC Infect Dis. 2015-2-19

[2]
CD8+ T cells in cutaneous leishmaniasis: the good, the bad, and the ugly.

Semin Immunopathol. 2015-5

[3]
Protective and pathological functions of CD8+ T cells in Leishmania braziliensis infection.

Infect Immun. 2015-3

[4]
Discrimination of T-cell subsets and T-cell receptor repertoire distribution.

Immunol Res. 2014-1

[5]
Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

PLoS Pathog. 2013-7-18

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CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis.

J Invest Dermatol. 2013-1-15

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Front Immunol. 2012-6-8

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PLoS One. 2012-5-31

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Accurate detection of the tumor clone in peripheral T-cell lymphoma biopsies by flow cytometric analysis of TCR-Vβ repertoire.

Mod Pathol. 2012-5-25

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Am J Trop Med Hyg. 2011-7

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