Asnagli H, Schmitt-Verhulst A M, Guimezanes A
Center for Immunology, INSERM-CNRS of Marseille-Luminy, France.
J Immunol. 1997 May 15;158(10):4533-42.
CD4+ and CD8+ T cells emerge from thymic selection expressing a TCR restricted by MHC class II (TCRII) and MHC class I (TCRI), and upon Ag stimulation develop respectively into Th and CTL effector cells. The influence of thymic differentiation and antigenic stimulation on the determination of T cell functions was studied, with CD4+ T cells expressing a transgenic TCRI that reacts with the class I alloantigen H-2K(b) in a CD8-independent fashion. Such T cells additionally express a TCR, probably TCRII, in which the transgenic TCR beta-chain is associated with endogenously rearranged TCR alpha-chains. Upon in vitro stimulation with H-2K(b)-expressing cells, both CD8+ and CD4+ transgenic TCR+ T cells developed into CTL capable of killing Ag-expressing target cells through a perforin-dependent mechanism, and secreted IL-2 and IFN-gamma. Fas ligand-dependent killing could also be induced in both CD8+ and CD4+ in vitro stimulated T cells. The capacity to secrete IL-4 was restricted to the CD4+ T cells, however, suggesting that both CD8/CD4-shared and CD4-unique programs can be elicited by stimulation of CD4 T cells through a TCRI. Acquisition of CTL function was also induced upon class II alloantigen stimulation through the endogenously rearranged TCRII, which represents a polyclonal set of TCRs. IL-2, IFN-gamma, and after restimulation, IL-4, were also produced. Thus: 1) events associated with intrathymic selection influence the gene program activated in response to the same TCRI/APC interaction; and 2) CD4+ T cells expressing a TCRI and a TCRII can activate the same gene program after engagement of either one of these TCRs.
CD4+和CD8+ T细胞经胸腺选择后出现，表达受MHC II类分子（TCRII）和MHC I类分子（TCRI）限制的TCR，并且在抗原刺激下分别发育为Th和CTL效应细胞。研究了胸腺分化和抗原刺激对T细胞功能确定的影响，其中CD4+ T细胞表达一种转基因TCRI，该TCRI以不依赖CD8的方式与I类同种异体抗原H-2K(b)反应。此类T细胞还额外表达一种TCR，可能是TCRII，其中转基因TCR β链与内源性重排的TCR α链相关。在用表达H-2K(b)的细胞进行体外刺激后，CD8+和CD4+转基因TCR+ T细胞均发育为CTL，能够通过穿孔素依赖机制杀伤表达抗原的靶细胞，并分泌IL-2和IFN-γ。在体外刺激的CD8+和CD4+ T细胞中也可诱导Fas配体依赖性杀伤。然而，分泌IL-4的能力仅限于CD4+ T细胞，这表明通过TCRI刺激CD4 T细胞可引发CD8/CD4共享和CD4独特的程序。通过内源性重排的TCRII（代表一组多克隆TCR）进行II类同种异体抗原刺激后，也可诱导CTL功能的获得。还产生了IL-2、IFN-γ，再次刺激后还产生了IL-4。因此：1）与胸腺内选择相关的事件会影响因相同TCRI/APC相互作用而激活的基因程序；2）表达TCRI和TCRII的CD4+ T细胞在这些TCR中的任何一个结合后均可激活相同的基因程序。
