CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
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DOI：
10.1038/nature01152
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发表时间：
2002-12-05
期刊：
影响因子：
64.8
通讯作者：
Sacks, DL
中科院分区：
文献类型：
--
作者：
Belkaid, Y;Piccirillo, CA;Sacks, DL
病原体在宿主体内的长期持续存在，也能够对再感染保持强大的抵抗力，称为伴随免疫，是某些传染病的标志，包括结核病和利什曼病。病原体在免疫个体中建立潜伏期的能力通常对疾病再激活具有严重后果（1-3）。在这里，我们表明，在耐药的C57 BL/6小鼠愈合后，皮肤中的主要利什曼原虫的持久性是由内源性CD 4（+）CD 25（+）调节性T细胞群体控制的。这些细胞占幼稚小鼠和人类外周CD 4（+）T细胞的5-10%，并抑制体内几种潜在的致病性应答，特别是针对自身抗原的T细胞应答（4）。在感染L.主要是CD 4（+）CD 25（+）T细胞在真皮中积聚，在真皮中它们通过白介素-10依赖性和白介素-10非依赖性机制抑制CD 4（+）CD 25（-）效应T细胞从该部位消除寄生虫的能力。在IL-10活性受损的小鼠中实现的杀菌免疫随后是对再感染的免疫力丧失，这表明在慢性感染部位的效应T细胞和调节T细胞之间建立的平衡可能反映了寄生虫和宿主的生存策略。
The long-term persistence of pathogens in a host that is also able to maintain strong resistance to reinfection, referred to as concomitant immunity, is a hallmark of certain infectious diseases, including tuberculosis and leishmaniasis. The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation(1-3). Here we show that the persistence of Leishmania major in the skin after healing in resistant C57BL/6 mice is controlled by an endogenous population of CD4(+)CD25(+) regulatory T cells. These cells constitute 5-10% of peripheral CD4(+) T cells in naive mice and humans, and suppress several potentially pathogenic responses in vivo, particularly T-cell responses directed against self-antigens(4). During infection by L. major, CD4(+)CD25(+) T cells accumulate in the dermis, where they suppress-by both interleukin-10-dependent and interleukin-10-independent mechanisms-the ability of CD4(+)CD25(-) effector T cells to eliminate the parasite from the site. The sterilizing immunity achieved in mice with impaired IL-10 activity is followed by the loss of immunity to reinfection, indicating that the equilibrium established between effector and regulatory T cells in sites of chronic infection might reflect both parasite and host survival strategies.