Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
J Immunol. 2010 Jan 1;184(1):351-8. doi: 10.4049/jimmunol.0902152. Epub 2009 Nov 30.
The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host-pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium-infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium. The observation that thymic infection interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific Ags, is of relevance to understand the immune response during chronic persistent infections. In addition, it has potential implications for the repertoire of T cells generated in patients with a mycobacterial infection recovering from severe lymphopenia, such as patients coinfected with HIV and receiving antiretroviral therapy.
胸腺产生大多数自身限制和自身耐受的 T 细胞群体的能力在很大程度上取决于分化过程中遇到的抗原。我们最近表明，分枝杆菌会传播到胸腺，这就提出了分枝杆菌在胸腺内如何影响 T 细胞分化以及这种影响是否会影响宿主-病原体相互作用的问题。无胸腺裸鼠用来自感染分枝杆菌的供体或对照未感染的供体的胸腺移植物重建。来自感染供体的胸腺产生的 T 细胞似乎通常是正常的，因为它们保留了重建外周的能力，并能够在体外对非特异性刺激以及在体内免疫接种时对第三方抗原（如 OVA）的抗原刺激作出反应。然而，这些细胞无法对分枝杆菌的挑战产生保护性免疫反应。胸腺感染干扰 T 细胞分化，产生对病原体特异性抗原耐受的 T 细胞的观察结果，对于理解慢性持续性感染期间的免疫反应具有重要意义。此外，它对于从严重淋巴细胞减少症中恢复的分枝杆菌感染患者（例如同时感染 HIV 并接受抗逆转录病毒治疗的患者）中产生的 T 细胞 repertoire 具有潜在影响。
