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