Perturbation and proinflammatory type activation of Vδ1+ γδ T cells in African children with Plasmodium falciparum malaria
Perturbation and proinflammatory type activation of Vδ1+ γδ T cells in African children with Plasmodium falciparum malaria
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DOI：
10.1128/iai.69.5.3190-3196.2001
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发表时间：
2001-05-01
影响因子：
3.1
通讯作者：
Behr, C
中科院分区：
文献类型：
--
作者：
Hviid, L;Kurtzhals, JAL;Behr, C
γ δ T细胞已经以各种方式涉及对疟疾的保护和疟疾的发病机制，但是很少有研究检测了非洲儿童中γ δ T细胞对疟疾的应答，非洲儿童遭受了绝大多数疟疾相关的发病率和死亡率。这是不幸的，因为现有的数据表明，从非免疫成人离体和体外研究中得出的结论的简单外推并不总是可能的。在这里，我们表明，频率和绝对数量的γ δ T细胞是短暂的增加治疗恶性疟原虫疟疾在加纳儿童和他们可以构成30至50%的所有T细胞后不久开始抗疟化疗。参与这种扰动的大部分γ δ T细胞表达V δ 1，并具有高度活化的表型。在V δ 1（+）细胞群体增加的峰值时对V δ 1（+）细胞群体的T细胞受体（TCR）的分析表明，使用了所有表达的V γ链，并且CDR 3长度多态性表明扩增的V δ 1群体是高度多克隆的。非常高比例的V delta 1（+）T细胞产生γ干扰素，而产生肿瘤坏死因子α的V delta 1（+）细胞比所有CD 3（+）细胞的平均比例少。在TCR-γ δ（+）细胞或V δ 1（+）细胞中未检测到白细胞介素10的产生。总之，我们的数据表明，在这组半免疫恶性疟原虫疟疾患者中，扩增的V δ 1（+）T细胞群具有免疫调节作用。
gamma delta T cells have variously been implicated in the protection against, and the pathogenesis of, malaria, but few studies have examined the gamma delta T-cell response to malaria in African children, who suffer the large majority of malaria associated morbidity and mortality. This is unfortunate, since available data suggest that simple extrapolation of conclusions drawn from studies of nonimmune adults ex vivo and in vitro is not always possible. Here we show that both the frequencies and the absolute numbers of gamma delta T cells are transiently increased following treatment of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta1 and had a highly activated phenotype. Analysis of the T-cell receptors (TCR) of the V delta1(+) cell population at the peak of their increase showed that all expressed V gamma chains were used, and CDR3 length polymorphism indicated that the expanded V delta1 population was highly polyclonal. A very high proportion of the V delta1(+) T cells produced gamma interferon, while fewer V delta1(+) cells than the average proportion of all CD3(+) cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-gamma delta (+) cells in general or V delta1(+) cells in particular. Taken together, our data point to an immunoregulatory role of the expanded V delta1(+) T-cell population in this group of semi-immune P, falciparum malaria patients.