Moore N C, Anderson G, McLoughlin D E, Owen J J, Jenkinson E J
Center for Clinical Research in Immunology and Signalling, Medical School, University of Birmingham, United Kingdom.
J Immunol. 1994 May 15;152(10):4826-31.
Despite the important role played by endogenous superantigen in shaping the T cell repertoire, little is known concerning the expression of the different Mtv loci in cells of the thymic microenvironment involved in repertoire selection. Here we have examined the expression of a panel of Mtv Ags by different MHC class II+ stromal cel types using reverse transcriptase-PCR and monitored the effects of these stromal cells on the development of cells expressing Mtv-reactive TCR V beta elements in closed thymic organ culture systems. Although Mtv-6 and Mtv-8/9 mRNAs are expressed in normal thymus lobe organ cultures, no Mtv expression was detected in MHC class II+ thymic epithelial cells. In contrast a striking pattern of differential expression was observed in dendritic cells of thymic origin that were devoid of Mtv-8/9 but expressed readily detectable levels of Mtv-6. This pattern of Mtv gene expression correlated well with TCR V beta repertoire development. TCRV beta 3+ T cells, normally deleted in response to Mtv-6, were virtually absent from the single positive thymocyte compartment in thymic organ cultures where dendritic cells are present but were present in reaggregate cultures where the only MHC class II-positive cells were thymic epithelial cells. On the other hand, V beta 11+ T-cells were not deleted in organ cultures, possibly reflecting the absence of Mtv-8/9 expression in dendritic cells. Our studies suggest that the influence Mtvs have on shaping the T cell repertoire not only depends on their expression within a particular strain but also on their tissue specific expression in relation to MHC class II, which is necessary for their presentation.
尽管内源性超抗原在塑造T细胞库中发挥着重要作用,但对于参与库选择的胸腺微环境细胞中不同Mtv基因座的表达情况却知之甚少。在此,我们利用逆转录聚合酶链反应检测了不同MHC II类+基质细胞类型中一组Mtv抗原的表达,并在封闭的胸腺器官培养系统中监测了这些基质细胞对表达Mtv反应性TCR Vβ元件的细胞发育的影响。虽然Mtv-6和Mtv-8/9 mRNA在正常胸腺叶器官培养物中表达,但在MHC II类+胸腺上皮细胞中未检测到Mtv表达。相反,在源自胸腺的树突状细胞中观察到明显的差异表达模式,这些细胞缺乏Mtv-8/9,但表达易于检测到的Mtv-6水平。这种Mtv基因表达模式与TCR Vβ库的发育密切相关。通常因Mtv-6而缺失的TCRVβ3+ T细胞,在存在树突状细胞的胸腺器官培养物的单阳性胸腺细胞区室中几乎不存在,但在仅MHC II类阳性细胞为胸腺上皮细胞的重聚集培养物中存在。另一方面,Vβ11+ T细胞在器官培养物中未被缺失,这可能反映了树突状细胞中不存在Mtv-8/9表达。我们的研究表明,Mtv对塑造T细胞库的影响不仅取决于它们在特定品系中的表达,还取决于它们与MHC II类相关的组织特异性表达,这对于它们的呈递是必要的。