Buzoni-Gatel D, Lepage A C, Dimier-Poisson I H, Bout D T, Kasper L H
Immunology of Infectious Diseases (CJF INSERM 93-09), Equipe associée INRA (Institut National de la Recherche Agronomique) d'Immunologie Parasitaire, Tours, France.
J Immunol. 1997 Jun 15;158(12):5883-9.
Intraepithelial lymphocytes (IEL) of the gut represent a primary immune barrier against infection by orally acquired pathogens. Naturally acquired infection with Toxoplasma gondii induces the proliferation of CD8+ T cells in both the gut and spleen. Gut-derived CD8alpha/beta+ IEL exhibit MHC-restricted cytotoxicity against parasite-infected enterocytes and macrophages. In a murine model, we demonstrate that the adoptive transfer of IEL obtained from inbred mice at day 11 postinfection is able to protect against a virulent challenge in syngenic recipients. In CBA mice, the parasite cyst load within the brain of the recipients receiving primed IEL was reduced by 90%. In BALB/c and C57BL/6 mice, a 50% decrease in mortality was observed following adoptive transfer of primed IEL. To determine the T cell subset responsible for protective immunity, a purified CD8alpha/beta+ IEL population was isolated from infected mice at day 11 postinfection. These cells were able to protect naive mice by adoptive transfer against a lethal parasite challenge. RNA analysis by reverse-transcriptase PCR revealed that primed CD8alpha/beta+ IEL produce significant message for IFN-gamma, an essential cytokine for host protection against toxoplasmosis. Administration of anti-IFN-gamma at the time of adoptive transfer of primed IEL abrogated protection. The adoptive transfer of these protective IEL was not restricted to the Ld class I locus. These data demonstrate that IFN-gamma-producing IEL may be an important primary barrier against acute and perhaps recurrent infection with T. gondii.
肠道上皮内淋巴细胞（IEL）是抵御经口感染病原体的主要免疫屏障。自然感染弓形虫会诱导肠道和脾脏中的CD8⁺ T细胞增殖。源自肠道的CD8α/β⁺ IEL对寄生虫感染的肠上皮细胞和巨噬细胞表现出MHC限制的细胞毒性。在小鼠模型中，我们证明在感染后第11天从近交系小鼠获得的IEL的过继转移能够保护同基因受体免受强毒株攻击。在CBA小鼠中，接受致敏IEL的受体小鼠脑内的寄生虫包囊负荷降低了90%。在BALB/c和C57BL/6小鼠中，过继转移致敏IEL后观察到死亡率降低了50%。为了确定负责保护性免疫的T细胞亚群，在感染后第11天从感染小鼠中分离出纯化的CD8α/β⁺ IEL群体。这些细胞能够通过过继转移保护未感染的小鼠免受致命的寄生虫攻击。逆转录酶PCR的RNA分析显示，致敏的CD8α/β⁺ IEL产生大量的IFN-γ信息，IFN-γ是宿主抵御弓形虫病的必需细胞因子。在过继转移致敏IEL时给予抗IFN-γ可消除保护作用。这些保护性IEL的过继转移不限于Ld I类基因座。这些数据表明，产生IFN-γ的IEL可能是抵御急性弓形虫感染以及可能抵御复发性感染的重要主要屏障。
