CD4 cell priming and tolerization are differentially programmed by APCs upon initial engagement
CD4 cell priming and tolerization are differentially programmed by APCs upon initial engagement
复制标题
DOI：
10.4049/jimmunol.168.11.5573
复制
发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Adler, AJ
中科院分区：
文献类型：
--
作者：
Higgins, AD;Mihalyo, MA;Adler, AJ
骨髓来源的APC以分别引起T细胞耐受或免疫的方式呈现实质自身和病原体来源的AGS。为了研究产生耐受性和免疫性APC功能的参数，我们使用了一种过继转移系统，在该系统中，原始的TCR转基因血凝素(HA)特异性的CD4(+)T细胞在遇到HA时被耐受，或者在遇到瞬时表达的痘苗衍生HA(病毒-HA)时被准备好表达效应功能。当病毒-HA呈现的持续时间延长到诱导对自身HA的耐受性所需的时间时，CD4细胞对病毒-HA的耐受性没有发生。此外，在耐受和启动的早期阶段，CD4细胞表现出表型和功能上的差异，这表明这些分化过程在最初的APC-CD4细胞相互作用后不久就被编程。当表达自身HA的小鼠感染无关的疫苗时，仍然发生了对CD4细胞的耐受，这表明启动和耐受不能用直接作用于CD4细胞的病原体诱导的第三方(即非APC)来解释。综上所述，这些结果表明，CD4细胞对实质自身AGS的耐受和对病原体来源的AGS的启动是由功能不同的APC启动的。
Bone marrow-derived APCs present both parenchymal-self and pathogen-derived Ags in a manner that elicits either T cell tolerization or immunity, respectively. To study the parameters that confer tolerogenic vs immunogenic APC function we used an adoptive transfer system in which naive TCR transgenic hemagglutinin (HA)-specific CD4(+) T cells are either tolerized upon encountering HA expressed constitutively as a parenchymal self-Ag (self-HA) or primed to express effector function upon encountering transiently expressed vaccinia-derived HA (viral-HA). When the duration of viral-HA presentation was extended for the period required to elicit tolerization toward self-HA, CD4 cell tolerization to viral-HA did not occur. Furthermore, CD4 cells exhibited both phenotypic as well as functional differences during early stages of tolerization and priming, suggesting that these divergent differentiation processes are programmed soon after the initial APC-CD4 cell interaction. When mice expressing self-HA were infected with an irrelevant vaccinia, CD4 cell tolerization still occurred, indicating that priming vs tolerization cannot be explained by pathogen-induced third parties (i.e., non-APCs) that act directly on CD4 cells. Taken together, these results suggest that CD4 cell tolerization to parenchymal self-Ags and priming to pathogen-derived Ags are initiated by functionally distinct APCs.