T Cells Specific to Leishmania and Other Nonrelated Microbial Antigens Can Migrate to Human Leishmaniasis Skin Lesions

T Cells Specific to Leishmania and Other Nonrelated Microbial Antigens Can Migrate to Human Leishmaniasis Skin Lesions
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DOI:
10.1038/jid.2009.428
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发表时间:
2010-05-01
影响因子:
6.5
通讯作者:
Coutinho, Sergio G.
Coutinho, Sergio G.
中科院分区:
医学1区
文献类型:
--
作者:
Da-Cruz, Alda M.;Oliveira-Neto, Manoel P.;Coutinho, Sergio G.

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免疫病理学研究有助于表征皮肤利什曼病(CL)的原位炎症浸润。然而,对这些病变的t细胞抗原反应性知之甚少。我们的目的是分析淋巴细胞从CL病变对利什曼原虫和非相关抗原的增殖和细胞因子的产生的反应性。从感染巴西利什曼原虫(Viannia)的CL患者的病变和血液中提取单核细胞。活化细胞占病变t细胞亚群的35-45%。C1.7/CD244(+)CD8(+) T细胞水平升高提示存在原位细胞毒效应。从利什曼病病变中分离的淋巴细胞增殖并产生ifn - γ,以响应利什曼抗原以及不相关的抗原,如弓形虫(Tg)。病变越大的患者淋巴细胞增殖指数最高。通过极限稀释试验在病变中检测到高频率的tg特异性细胞,类似于利什曼特异性细胞的频率。重要的是,没有弓形虫病病史的患者的病变中没有发现tg反应细胞。利什曼反应性CD4(+)和CD8(+) T细胞在病变中的比例变化很大。总的来说,这些数据表明,T细胞对非相关抗原的反应可以迁移到利什曼病病变,并可能影响疾病的发病机制。
Immunopathological studies have contributed to the characterization of in situ inflammatory infiltrates in cutaneous leishmaniasis (CL). However, little is known about the T-cell antigen reactivity of these lesions. Our objective was to analyze the responsiveness of lymphocytes from CL lesions to leishmanial and nonrelated antigens in terms of proliferation and the production of cytokines. Mononuclear cells were extracted from lesions, and blood from CL patients infected with Leishmania (Viannia) braziliensis. Activated cells accounted for 35-45% of lesions T-cell subsets. Elevated levels of C1.7/CD244(+)CD8(+) T cells suggest in situ cytotoxic effector function. Lymphocytes isolated from the leishmaniasis lesions proliferated and produced IFN-gamma in response to leishmanial antigens as well as to irrelevant antigens such as Toxoplasma gondii (Tg). Patients presenting with larger lesions had the highest lymphocyte proliferation indexes. A high frequency of Tg-specific cells was detected in the lesions by limiting dilution assay, similar to the frequency of Leishmania-specific cells. Importantly, Tg-reactive cells were not found in lesions of patients without a history of toxoplasmosis. The proportion of Leishmania-reactive CD4(+) and CD8(+) T cells in the lesions was quite variable. Overall, these data suggest that T cells reactive to nonrelevant antigens can migrate to leishmanial lesions and possibly influence the pathogenesis of the disease.