Essential role of extrathymic T cells in protection against malaria

Essential role of extrathymic T cells in protection against malaria
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DOI:
10.4049/jimmunol.169.1.301
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发表时间:
2002-07-01
影响因子:
4.4
通讯作者:
Abo, T
Abo, T
中科院分区:
医学2区
文献类型:
--
作者:
Mannoor, MK;Halder, RC;Abo, T

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胸腺裸小鼠既不携带传统的T细胞,也不携带来自胸腺的NKT细胞。然而,NK1.1(-)TCR(int)细胞存在于胸腺小鼠的肝脏和其他免疫器官中,因为这些淋巴细胞亚群确实起源于胸腺外。在这项研究中,我们检测了胸腺外T细胞是否具有保护小鼠免受疟疾感染的能力。虽然B6-nu/nu小鼠比对照B6小鼠对疟疾更敏感,但当注入较少数量的寄生红细胞(每只小鼠5 X 10(3))时,这些胸腺发育小鼠能够在疟疾中存活。暴发期肝脏出现淋巴细胞增多,主要扩增淋巴细胞为NK1.1(-)TCR(in)t细胞(IL-2Rbeta(+)TCRalphabeta(+))。非常规CD8(+) NKT细胞(Valpha14(-))也出现。与B6小鼠的情况类似,疟疾感染期间出现了针对变性DNA的自身抗体(IgM型)。在进行细胞转移实验时,从疟疾康复的胸腺小鼠肝脏中分离出的免疫淋巴细胞能够保护辐照的胸腺和胸腺小鼠免受疟疾的侵害。结合之前在无胸腺小鼠中的结果,目前在无胸腺小鼠中的结果表明,与疟疾保护相关的主要淋巴细胞亚群可能是胸腺外T细胞。
Athymic nude mice carry neither conventional T cells nor NKT cells of thymic origin. However, NK1.1(-)TCR(int) cells are present in the liver and other immune organs of athymic mice, because these lymphocyte subsets are truly of extrathymic origin. In this study, we examined whether extrathymic T cells had the capability to protect mice from malarial infection. Although B6-nu/nu mice were more sensitive to malaria than control B6 mice, these athymic mice were able to survive malaria when a reduced number of parasitized erythrocytes (5 X 10(3) per mouse) were injected. At the fulminant stage, lymphocytosis occurred in the liver and the major expanding lymphocytes were NK1.1(-)TCR(in)t cells (IL-2Rbeta(+)TCRalphabeta(+)). Unconventional CD8(+) NKT cells (Valpha14(-)) also appeared. Similar to the case of B6 mice, autoantibodies (IgM type) against denatured DNA appeared during malarial infection. Immune lymphocytes isolated from the liver of athymic mice which had recovered from malaria were capable of protecting irradiated euthymic and athymic mice from malaria when cell transfer experiments were conducted. In conjunction with the previous results in euthymic mice, the present results in athymic mice suggest that the major lymphocyte subsets associated with protection against malaria might be extrathymic T cells.