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效应记忆CD4(+) T细胞根据美洲皮肤利什曼病损伤的持续时间差异表达激活相关分子。

Effector memory CD4(+) T cells differentially express activation associated molecules depending on the duration of American cutaneous leishmaniasis lesions.

作者信息

de Oliveira Mendes-Aguiar C, Vieira-Gonçalves R, Guimarães L H, de Oliveira-Neto M P, Carvalho E M, Da-Cruz A M

机构信息

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro.

Serviço de Imunologia, Hospital Universitário Edgar Santos-UFBA.

出版信息

Clin Exp Immunol. 2016 Aug;185(2):202-9. doi: 10.1111/cei.12798. Epub 2016 Jun 6.

Abstract

A high number of Leishmania-responder T cells is found in cutaneous leishmaniasis lesions, suggesting that important immunological events occur at the site of infection. Although activated, cytotoxic and regulatory T cells infiltrating into lesions may influence disease pathogenesis, the role of the T cell differentiation pattern of lymphocytes in lesions is unknown. Our aim was to investigate whether the phase of lesion development (early or late) is influenced by the functional status of cells present in inflammatory infiltrate. Activation, cytotoxity and T cell differentiation molecules were evaluated in lesion mononuclear cells by flow cytometry. The frequency of T cells was correlated with the lesion area (r = 0·68; P = 0·020). CD4(+) CD25(+) T cells predominated over CD4(+) CD69(+) T cells in early lesions (less than 30 days), whereas late lesions (more than 60 days) exhibited more CD4(+) CD69(+) T cells than CD4(+) CD25(+) T cells. The duration of illness was correlated positively with CD4(+) CD69(+) (r = 0·68; P = 0·005) and negatively with CD4(+) CD25(+) T cells (r = -0·45; P = 0·046). Most CD8(+) T cells expressed cytotoxic-associated molecules (CD244(+) ), and the percentages were correlated with the lesion area (r = 0·52; P = 0·04). Both CD4(+) and CD8(+) effector memory T cells (TEM -CD45RO(+) CCR7(-) ) predominated in CL lesions and were significantly higher than central memory (TCM -CD45RO(+) CCR7(+) ) or naive T cells (CD45RO(-) CCR7(+) ). An enrichment of TEM cells and contraction of naive T cells were observed in lesions in comparison to blood (P = 0·006) for both CD4(+) and CD8(+) T cells. Lesion chronicity is associated with a shift in activation phenotype. The enrichment of TEM and activated cytotoxic cells can contribute to immune-mediated tissue damage.

摘要

在皮肤利什曼病病变中发现大量对利什曼原虫有反应的T细胞,这表明在感染部位发生了重要的免疫事件。尽管浸润到病变中的活化、细胞毒性和调节性T细胞可能影响疾病发病机制,但病变中淋巴细胞的T细胞分化模式的作用尚不清楚。我们的目的是研究病变发展阶段(早期或晚期)是否受炎症浸润中细胞功能状态的影响。通过流式细胞术评估病变单核细胞中的活化、细胞毒性和T细胞分化分子。T细胞频率与病变面积相关(r = 0·68;P = 0·020)。在早期病变(少于30天)中,CD4(+) CD25(+) T细胞多于CD4(+) CD69(+) T细胞,而晚期病变(超过60天)中CD4(+) CD69(+) T细胞比CD4(+) CD25(+) T细胞更多。病程与CD4(+) CD69(+) 呈正相关(r = 0·68;P = 0·005),与CD4(+) CD25(+) T细胞呈负相关(r = -0·45;P = 0·046)。大多数CD8(+) T细胞表达细胞毒性相关分子(CD244(+) ),其百分比与病变面积相关(r = 0·52;P = 0·04)。CD4(+) 和CD8(+) 效应记忆T细胞(TEM -CD45RO(+) CCR7(-) )在皮肤利什曼病病变中占主导地位,且显著高于中央记忆T细胞(TCM -CD45RO(+) CCR7(+) )或初始T细胞(CD45RO(-) CCR7(+) )。与血液相比,在病变中观察到CD4(+) 和CD8(+) T细胞的效应记忆T细胞富集和初始T细胞减少(P = 0·006)。病变的慢性化与活化表型的转变有关。效应记忆T细胞和活化细胞毒性细胞的富集可导致免疫介导的组织损伤。

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