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在成功的T细胞依赖性肿瘤免疫治疗过程中T细胞无反应性的矛盾存在:小隐孢子虫全身给药后T细胞“失忆”状态的特征

Paradoxical presence of T cell anergy during successful T cell-dependent tumour immunotherapy: characterization of a state of T cell 'amnaesia' following systemic administration of C. parvum.

作者信息

McBride W H, Howie S

出版信息

Clin Exp Immunol. 1984 Jul;57(1):139-48.

Abstract

Systemic administration of Corynebacterium parvum causes T cell-dependent regression of an established methylcholanthrene-induced murine fibrosarcoma beginning 10 days after Cp injection. At this time, tumour specific effector T cell responses measured by reactivity in a T helper cell assay or in a Winn assay disappear only to return later. We refer to this temporary lapse in T cell reactivity as immunological 'amnaesia'. Antigen specific T cell responses within all lymphoid organs appear to be affected. The 'amnaesic' state is characterised by the presence of primed T cells but the absence of T effector cells and suppressor cells. The differentiation of the primed T cells is blocked probably as a result on the non-delivery of a differentiation signal. There are several possible mechanisms which could account for this; the one we prefer is that cells are prevented from entering T cell-dependent cell interaction areas within lymphoid organs. This state of T cell 'amnaesia' may underlie anergy in some inflammatory, infectious and neoplastic diseases. The apparent paradox of T cell-dependent tumour regression occurring in mice with depressed T cell responses is discussed.

摘要

全身性给予短小棒状杆菌可使已建立的甲基胆蒽诱导的小鼠纤维肉瘤在注射短小棒状杆菌10天后出现T细胞依赖性消退。此时,通过T辅助细胞测定或温氏试验中的反应性测量的肿瘤特异性效应T细胞反应消失,随后才恢复。我们将T细胞反应性的这种暂时缺失称为免疫“遗忘”。所有淋巴器官内的抗原特异性T细胞反应似乎都受到影响。“遗忘”状态的特征是存在致敏T细胞,但缺乏T效应细胞和抑制细胞。致敏T细胞的分化可能由于未传递分化信号而受阻。有几种可能的机制可以解释这一点;我们倾向的一种机制是细胞被阻止进入淋巴器官内的T细胞依赖性细胞相互作用区域。T细胞“遗忘”状态可能是某些炎症、感染和肿瘤性疾病中无反应性的基础。本文讨论了在T细胞反应性降低的小鼠中发生T细胞依赖性肿瘤消退这一明显矛盾的现象。

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