Center for Immunology, University of Minnesota, Saint Paul, United States.
Minnesota Supercomputing Institute, University of Minnesota, Saint Paul, United States.
Elife. 2021 Apr 30;10:e65615. doi: 10.7554/eLife.65615.
Self-specific CD8T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8 T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in , which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/K-specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to -deficient () mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/K-specific cells showed blunted expansion and less readily differentiated into a CD25proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/K-specific cells mediated vitiligo much less efficiently. Hence, CD8 T cell self-specificity is poorly predicted by precursor frequency, phenotype, or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.
自身特异性 CD8T 细胞可以逃避克隆删除，但在生理环境中此类细胞的特性和功能尚不清楚。我们对表达或缺乏这种酶（由于编码 Trp2 的 缺失）的小鼠中的黑素细胞抗原酪氨酸酶相关蛋白 2 (Trp2) 多克隆 CD8T 细胞进行了表征。未免疫的 Trp2/K 特异性细胞的表型和基因表达谱相似；与野生型（WT）相比，该群体的大小仅略有减少（-deficient () 小鼠）。尽管对 Trp2 免疫接种的初始反应相当，但 WT Trp2/K 特异性细胞的扩增受到抑制，并且更不容易分化为 CD25 增殖群体。在评估免疫病理学时，明显出现了功能性自身耐受性：过继转移的 WT Trp2/K 特异性细胞介导的白癜风效率要低得多。因此，CD8T 细胞的自身特异性不能仅通过前体频率、表型甚至初始反应性来预测，而激活诱导的 CD25 表达和其他基因表达特征的缺陷可能有助于识别功能上耐受的细胞。
