Belkaid Yasmine, Piccirillo Ciriaco A, Mendez Susana, Shevach Ethan M, Sacks David L
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature. 2002 Dec 5;420(6915):502-7. doi: 10.1038/nature01152.
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. 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. 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.
病原体在宿主中长期持续存在，而宿主又能够维持对再感染的强大抵抗力，这种情况被称为伴随免疫，是包括结核病和利什曼病在内的某些传染病的一个标志。病原体在免疫个体中建立潜伏状态的能力通常会对疾病复发产生严重后果。在此，我们表明，在抗性C57BL/6小鼠愈合后，皮肤中硕大利什曼原虫的持续存在受内源性CD4+CD25+调节性T细胞群体控制。这些细胞在未接触过抗原的小鼠和人类外周CD4+T细胞中占5%-10%，并在体内抑制几种潜在的致病反应，特别是针对自身抗原的T细胞反应。在硕大利什曼原虫感染期间，CD4+CD25+T细胞在真皮中积聚，在那里它们通过依赖白细胞介素-10和不依赖白细胞介素-10的机制，抑制CD4+CD25-效应T细胞从该部位清除寄生虫的能力。白细胞介素-10活性受损的小鼠实现的无菌免疫之后是对再感染的免疫力丧失，这表明在慢性感染部位效应T细胞和调节性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。
