Kanagawa O, Nakauchi H, Sekaly R P, Maeda K, Takagaki Y
Department of Pathology and Medicine, Washington University, St Louis, MO 63110.
Int Immunol. 1990;2(10):957-64. doi: 10.1093/intimm/2.10.957.
Expression and function of mouse and human CD8 (mCD8 and hCD8) alpha chain molecules in mouse T cell hybridomas were analyzed. The expression of cytolytic T lymphocyte-derived CD8 molecules was suppressed in hybridomas established by fusing the BW5147 thymoma to a CD8+ cytolytic T lymphocyte clone, while expression of CD4 remained intact in BW x CD4+ helper T cell hybridomas. However, hybridomas established by fusing a cytolytic T cell clone with BW5147 cell lines, transfected with either the mCD8 alpha or hCD8 alpha chain, expressed the T cell-derived mCD8 beta chain as a CD8 heterodimer (mCD8 alpha/mCD8 beta or hCD8 alpha/mCD8 beta). These data suggest that negative regulatory mechanisms for the mCD8 alpha gene in BW thymoma failed to suppress mCD8 beta gene expression, indicating different regulatory mechanisms for the tightly linked mCD8 alpha and mCD8 beta genes. Analysis of the antigen reactivity of the hybridomas revealed that the human CD8 alpha chain failed to increase the mouse T cell receptor - class I MHC interaction, even as a heterodimeric form with mCD8 beta molecules. However, both the human CD8 alpha homodimer and the heterodimeric form with mCD8 beta were found to be capable of suppressing the class II-restricted T cell response.
分析了小鼠和人类CD8(mCD8和hCD8)α链分子在小鼠T细胞杂交瘤中的表达及功能。通过将BW5147胸腺瘤与CD8⁺细胞毒性T淋巴细胞克隆融合建立的杂交瘤中,细胞毒性T淋巴细胞来源的CD8分子表达受到抑制,而在BW×CD4⁺辅助性T细胞杂交瘤中CD4表达保持完整。然而,通过将细胞毒性T细胞克隆与用mCD8α或hCD8α链转染的BW5147细胞系融合建立的杂交瘤,表达T细胞来源的mCD8β链作为CD8异二聚体(mCD8α/mCD8β或hCD8α/mCD8β)。这些数据表明,BW胸腺瘤中mCD8α基因的负调控机制未能抑制mCD8β基因表达,这表明紧密连锁的mCD8α和mCD8β基因存在不同的调控机制。对杂交瘤抗原反应性的分析表明,即使作为与mCD8β分子的异二聚体形式,人类CD8α链也未能增强小鼠T细胞受体与I类MHC的相互作用。然而,发现人类CD8α同二聚体以及与mCD8β的异二聚体形式均能够抑制II类限制性T细胞反应。