Hare Katherine J, Pongracz Judit, Jenkinson Eric J, Anderson Graham
Department of Anatomy, Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom.
J Immunol. 2003 Sep 15;171(6):2825-31. doi: 10.4049/jimmunol.171.6.2825.
T cell receptor signaling in the thymus can result in positive selection, and hence progressive maturation to the CD4(+)8(-) or CD4(-)8(+) stage, or induction of apoptosis by negative selection. Although it is poorly understood how TCR ligation at the CD4(+)8(+) stage can lead to such different cell fates, it is thought that the strength of signal may play a role in determining the outcome of TCR signaling. In this study, we have characterized the formation of an active signaling complex in thymocytes undergoing positive selection as a result of interaction with thymic epithelial cells. Although this signaling complex involves redistribution of cell surface and intracellular molecules, reminiscent of that observed in T cell activation, accumulation of GM1-containing lipid rafts was not observed. However, enforced expression of the costimulatory molecule CD80 on thymic epithelium induced GM1 polarization in thymocytes, and was accompanied by reduced positive selection and increased apoptosis. We suggest that the presence or absence of CD80 costimulation influences the outcome of TCR signaling in CD4(+)8(+) thymocytes through differential lipid raft recruitment, thus determining overall signal strength and influencing developmental cell fate.
胸腺中的T细胞受体信号传导可导致阳性选择，进而逐步成熟至CD4(+)8(-)或CD4(-)8(+)阶段，或通过阴性选择诱导细胞凋亡。尽管目前对CD4(+)8(+)阶段的TCR连接如何导致如此不同的细胞命运了解甚少，但人们认为信号强度可能在决定TCR信号传导的结果中发挥作用。在本研究中，我们对与胸腺上皮细胞相互作用而经历阳性选择的胸腺细胞中活性信号复合物的形成进行了表征。尽管这种信号复合物涉及细胞表面和细胞内分子的重新分布，这让人联想到在T细胞活化中观察到的情况，但未观察到含GM1的脂筏的积累。然而，胸腺上皮细胞上共刺激分子CD80的强制表达诱导了胸腺细胞中的GM1极化，并伴随着阳性选择减少和细胞凋亡增加。我们认为，CD80共刺激的存在与否通过不同的脂筏募集影响CD4(+)8(+)胸腺细胞中TCR信号传导的结果，从而决定整体信号强度并影响发育细胞命运。
