Heath V L, Saoudi A, Seddon B P, Moore N C, Fowell D J, Mason D W
MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, Oxford.
J Autoimmun. 1996 Apr;9(2):241-6. doi: 10.1006/jaut.1996.0030.
Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extrathymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.
T细胞的自身耐受性被认为主要通过两种机制维持：针对在胸腺中表达的自身抗原的克隆清除，以及对那些仅在胸腺外表达的自身抗原的T细胞无能或T细胞无反应性。这些机制是被动的，因为它们依赖于自身反应性T细胞在成熟过程中被清除，或者在成熟后变得内在无反应。本文所呈现的数据表明，这一模式需要修正。首先，很明显，通常被视为组织特异性的自身抗原也可能在胸腺中表达，在那里它们会影响发育中的T细胞库。其次，似乎存在某种T细胞介导的调节机制，该机制会积极阻止潜在的自身反应性T细胞发挥其致病潜力。我们的数据表明，这种调节机制是在胸腺内建立的，并且是幼稚T细胞库的固有特性。根据目前已知的单个T细胞与激动剂和拮抗剂肽相互作用时的反应方式对该机制进行了讨论，并考虑了可能的治疗意义。
