Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8(+) T cells.

Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8(+) T cells.
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不依赖胸腺的自身抗原特异性 CD8( ) T 细胞的异常细胞毒活性。

DOI:
10.1093/intimm/12.12.1677
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发表时间:
2000
影响因子:
4.4
通讯作者:
K. Nomoto
K. Nomoto
中科院分区:
医学3区
文献类型:
--
作者:
H. Yamada;G. Matsuzaki;Y. Iwamoto;K. Nomoto

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我们比较了胸腺依赖性和胸腺非依赖性CD8(+)T细胞的细胞毒活性。具有外源抗原特异性的胸腺依赖性CD 8(+)T细胞在基础剂量的抗原肽下获得对肿瘤细胞的细胞毒性活性,并且仅在分化为效应细胞毒性T淋巴细胞(CTL)后才获得对表达抗TCR mAb的杂交瘤细胞的细胞毒性活性。相比之下,已经显示出自身抗原特异性的胸腺非依赖性CD8(+)T细胞从未显示出对具有基础剂量的自身抗原肽的靶细胞的细胞毒性活性,而它们甚至在没有预先抗原刺激的情况下也可以裂解表达抗TCR mAb的杂交瘤细胞。此外,还观察到胸腺非依赖性CD8(+)T细胞对具有高剂量抗原肽的靶细胞的离体细胞毒性活性,所述靶细胞不被新鲜分离的胸腺依赖性CD8(+)T细胞裂解。因此,这表明,胸腺非依赖性,自身抗原特异性的CD8(+)T细胞已经获得成熟的CTL功能在原位,但有一个增加的阈值TCR介导的信号激活。胸腺依赖性和胸腺非依赖性CD8(+)T细胞之间的细胞毒活性的这些差异表明了体内两种CD8(+)T细胞亚群的不同作用。
We compared the cytotoxic activities of thymus-dependent and thymus-independent CD8(+) T cells. Thymus-dependent CD8(+) T cells, which are foreign antigen specific, acquired cytotoxic activity to tumor cells with a basal dose of the antigen peptides and to hybridoma cells expressing anti-TCR mAb only after differentiation into effector cytotoxic T lymphocytes (CTL). In contrast, thymus-independent CD8(+) T cells, which have been shown to be self-antigen specific, never showed cytotoxic activity to the target cells with a basal dose of the self-antigen peptide, while they could lyse hybridoma cells expressing anti-TCR mAb even without prior antigenic stimulation. Furthermore, the ex vivo cytotoxic activity of thymus-independent CD8(+) T cells was also observed against the target cells with high doses of the antigen peptides, which were not lysed by freshly isolated thymus-dependent CD8(+) T cells. Thus it is revealed that thymus-independent, self-antigen-specific CD8(+) T cells already acquire mature CTL functions in situ but have an increased threshold of TCR-mediated signaling for activation. These differences in cytotoxic activities between thymus-dependent and thymus-independent CD8(+) T cells suggest distinct roles of the two subsets of CD8(+) T cells in vivo.
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