Burnet envisaged the early presence of self-antigens in development, or ‘the history’ of an animal, ablates the animal's ability to immunologically respond against them. Lederberg added the idea that the continuous presence of self-antigens is required to maintain tolerance throughout life. We refer to Lederberg's proposal as ‘The Historical Postulate’. The mechanism of central tolerance, as now understood, is consistent with The Historical Postulate. Some observations, reflecting peripheral tolerance, appear inconsistent with this postulate. For example, some foreign peripheral tissues, grafted onto an animal before the immune system develops, can be rejected as the immune system matures. The original two-signal model of lymphocyte activation was proposed in part because it accounted for peripheral tolerance in a manner consistent with The Historical Postulate. We proposed that lymphocyte activation required antigen-mediated lymphocyte cooperation, whereas antigen would inactivate lymphocytes when insufficient in number to achieve activation. We argue here that the exceptions to The Historical Postulate can be explained by the two-signal model of lymphocyte activation: they reflect the existence of greater numbers of lymphocytes specific for these antigens than for natural peripheral antigens, and so are outside the physiological limits important in selecting through evolution this mechanism of peripheral tolerance. We argue that a consideration of whether The Historical Postulate is valid is important, even if only valid within certain understandable limits. The currently popular DAMP model of CD4 T cell activation is, strictly speaking and in a manner we discuss, in violation of this postulate.

中文翻译：

---

历史假设：它是系统层面上自我非自我歧视的基础吗？

伯内特设想在发育过程中自身抗原的早期存在，或动物的“历史”，会消融动物对它们进行免疫反应的能力。Lederberg 补充说，自身抗原的持续存在是维持整个生命耐受性所必需的。我们将莱德伯格的提议称为“历史假设”。正如现在所理解的，中央容忍的机制与历史假设是一致的。一些反映外周耐受性的观察结果似乎与这一假设不一致。例如，一些在免疫系统发育之前移植到动物身上的外来外周组织，可能会随着免疫系统的成熟而被排斥。最初提出的淋巴细胞激活的双信号模型部分是因为它以与历史假设一致的方式解释了外周耐受。我们提出淋巴细胞激活需要抗原介导的淋巴细胞合作，而当数量不足以实现激活时，抗原会使淋巴细胞失活。我们在这里争辩说，历史假设的例外情况可以用淋巴细胞激活的双信号模型来解释：它们反映了对这些抗原的特异性淋巴细胞数量比天然外周抗原的数量要多，因此生理极限之外是重要的通过进化选择这种外周耐受机制。我们认为考虑历史假设是否有效很重要，即使仅在某些可以理解的范围内有效。目前流行的 CD4 T 细胞激活 DAMP 模型，严格来说，以我们讨论的方式，违反了这一假设。