A requirement for the Vγ1+ subset of peripheral γδ T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology
A requirement for the Vγ1+ subset of peripheral γδ T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology
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DOI：
10.4049/jimmunol.175.12.8191
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Carding, SR
中科院分区：
文献类型：
--
作者：
Egan, CE;Dalton, JE;Carding, SR
γ δ T细胞是广泛分布的不同T细胞群体，并且是病原体诱导的免疫应答的共同特征。然而，目前尚不清楚不同的γ δ T细胞群体是否具有特定的功能，以及哪些因素决定了个体群体的功能特性。用经口弓形虫感染的小鼠模型来确定V γ 1（+）肠上皮内淋巴细胞（IEL）与系统性V γ 1（+）T细胞对宿主免疫应答的急性和慢性阶段的贡献，以及在细菌感染中描述的V γ 1（+）T细胞的巨噬细胞杀伤活性是否在其他无关的感染性疾病模型中观察到。用强毒1型和无毒11型T.弓形虫-、TCR-δ（-/-）小鼠迅速发展为严重的回肠炎。相比之下，在缺乏V γ 1（+）T细胞和IEL的小鼠和野生型小鼠中，炎症的发作延迟且不太严重。（v γ 1（-））IEL对弓形虫感染的保护作用与其溶细胞和产生细胞因子（Th 1）的能力无关。系统性V γ 1（+）细胞显示在限制外周组织，特别是CNS中寄生虫生长和炎症中发挥重要作用，这与其有效杀死寄生虫引发和感染的巨噬细胞的能力有关。这些发现表明V γ 1（+）T细胞的巨噬细胞杀细胞活性可能是病原体诱导的免疫应答的普遍特征，并且微环境因素影响γ δ T细胞在宿主对感染的应答中的参与和功能。
gamma delta T cells are a diverse population of T cells that are widely distributed and are a common feature of pathogen-induced immune responses. It is not clear, however, whether different populations of gamma delta T cells have specific functions, and what factors determine the functional properties of individual populations. A murine model of peroral Toxoplasma gondii infection was used to determine the contribution V gamma 1(+) intestinal intraepithelial lymphocytes (IELs) vs systemic V gamma 1(+) T cells make to the acute and chronic stages of the host immune response, and whether the macrophage cytocidal activity of V gamma 1(+) T cells described in bacterial infections is seen in other, unrelated infectious disease models. In response to oral infection with virulent type 1 or avirulent type 11 strains of T. gondii-, TCR-delta(-/-) mice rapidly developed severe ileitis. In contrast, in mice deficient in V gamma 1(+) T cells and IELs and wild-type mice, inflammation was delayed in onset and less severe. The protective effect of (v gamma 1(-)) IELs to Toxoplasma infection was unrelated to their cytolytic and cytokine (Th1)-producing capabilities. Systemic V gamma 1(+) cells were shown to play an essential role in limiting parasite growth and inflammation in peripheral tissues and, in particular, in the CNS, that was associated with their ability to efficiently kill parasite-elicited and infected macrophages. These findings suggest that macrophage cytocidal activity of V gamma 1(+) T cells may be a universal feature of pathogen-induced immune responses and that microenvironmental factors influence the involvement and function of gamma delta T cells in the host response to infection.