Ting C C, Hargrove M E, Wunderlich J, Loh N N
Cell Immunol. 1987 Jan;104(1):115-25. doi: 10.1016/0008-8749(87)90012-8.
The present study was undertaken to examine the differential expression of asialo GM1 (AsGM1) on the responding cells and effectors of alloreactive cytotoxic T lymphocytes (CTL) and lymphokine-induced activated killers (LAK). It was found that AsGM1 was expressed on the 3-day-cultured LAK effectors. Its expression gradually disappeared to the extent that AsGM1 became undetectable after 5 to 6 days of culturing. In contrast, AsGM1 was detected on 3-day CTL generated in mixed-lymphocyte cultures (bulk cultures); however, the levels of AsGM1 expression remained the same for at least 7 days. When examining the expression of AsGM1 on the responding cells, the reciprocal results were obtained. AsGM1 was expressed the LAK responders, but we were unable to demonstrate AsGM1 on CTL responders. Depletion of AsGM1+ cells from the responding population reduced subsequent CTL responses; however, CTL responses could be restored by adding conditioned media containing both interleukin 2 (IL-2) and other helper-T-cell factors and could not be restored by purified IL-2 alone adding at comparable doses. Reconstituting the AsGM1-depleted responders with Lyt-2-depleted splenocytes also restored the CTL response. Furthermore, depletion of AsGM1 cells from the responding population did not reduce the precursor frequency of allo-CTL, whereas the precursor frequency of LAK cells was reduced 42-fold. These findings show that the reduction of CTL responses after depletion of AsGM1+ cells was not due to the removal of precursors; instead, the defect appeared to be in the helper population. We further found that the helper defect was not due to impaired IL-2 production, because the endogenous production of IL-2 AsGM1-depleted responders was not reduced. Therefore, AsGM1+ cells may play a role in the helper pathway other than IL-2 production.
本研究旨在检测去唾液酸GM1（AsGM1）在同种异体反应性细胞毒性T淋巴细胞（CTL）和淋巴因子诱导的活化杀伤细胞（LAK）的反应细胞及效应细胞上的差异表达。研究发现，AsGM1在培养3天的LAK效应细胞上表达。其表达逐渐消失，培养5至6天后AsGM1变得无法检测到。相比之下，在混合淋巴细胞培养（批量培养）中产生的3天CTL上可检测到AsGM1；然而，AsGM1的表达水平至少7天保持不变。在检测反应细胞上AsGM1的表达时，得到了相反的结果。AsGM1在LAK反应细胞上表达，但我们无法在CTL反应细胞上证明AsGM1的存在。从反应群体中去除AsGM1+细胞会降低随后的CTL反应；然而，通过添加含有白细胞介素2（IL-2）和其他辅助性T细胞因子的条件培养基可以恢复CTL反应，而以相当剂量单独添加纯化的IL-2则无法恢复。用Lyt-2缺陷的脾细胞重建AsGM1缺陷的反应细胞也能恢复CTL反应。此外，从反应群体中去除AsGM1细胞不会降低同种异体CTL的前体细胞频率，而LAK细胞的前体细胞频率降低了42倍。这些发现表明，去除AsGM1+细胞后CTL反应的降低不是由于前体细胞的去除；相反，缺陷似乎在于辅助细胞群体。我们进一步发现，辅助缺陷不是由于IL-2产生受损，因为AsGM1缺陷的反应细胞中IL-2的内源性产生并未减少。因此，AsGM1+细胞可能在除IL-2产生之外的辅助途径中发挥作用。
