Maraskovsky E, Troutt A B, Kelso A
Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
Int Immunol. 1992 Apr;4(4):475-85. doi: 10.1093/intimm/4.4.475.
Interaction between the cell adhesion molecules lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) augments T cell activation by increasing the avidity of T cell/antigen-presenting cell (APC) binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell activation in the absence of APCs, single murine CD4+ and CD8+ T cells were cultured with IL-2 and immobilized antibodies to CD3, CD4 or CD8, and LFA-1 or ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated approximately 20% of CD4+ cells and 30% of CD8+ cells to proliferate. Inclusion of anti-ICAM-1 antibody increased these frequencies to 30 and 40% respectively. Maximum activation frequencies were obtained with the combination of anti-CD3, anti-CD4/CD8, and anti-LFA-1 which stimulated cell division by approximately 40% of single CD4+ cells and at least 60% of single CD8+ cells. Under these conditions, 30-40% of the resultant CD4+ clones and greater than 90% of CD8+ clones secreted IL-3 and IFN-gamma. In addition to responding at higher frequencies that CD4+ cells, CD8+ cells formed larger clones which produced 4-fold higher levels of both cytokines. Although the expression of IL-2, IL-3, IFN-gamma, granulocyte-macrophage colony stimulating factor and tumor necrosis factor alpha could be detected in CD4+ and CD8+ clones at the mRNA level following reverse transcription and polymerase chain reaction amplification, neither the secreted nor mRNA expression of IL-4 or IL-6 was detected in any of the tested clones. It is concluded that co-stimulation of T cells via LFA-1 or ICAM-1 can enhance T cell receptor-dependent activation in the absence of accessory cells and that this mode of stimulation leads to the expression of a restricted range of cytokine genes.
细胞黏附分子淋巴细胞功能相关抗原-1（LFA-1）与细胞间黏附分子-1（ICAM-1）之间的相互作用，通过提高T细胞/抗原呈递细胞（APC）结合的亲和力来增强T细胞活化。为了研究在没有APC的情况下，LFA-1和ICAM-1是否也能促进T细胞活化，将单个小鼠CD4⁺和CD8⁺T细胞与白细胞介素-2（IL-2）以及固定化的抗CD3、抗CD4或抗CD8抗体，以及抗LFA-1或抗ICAM-1抗体一起培养。抗CD3、抗CD4/CD8和IL-2的组合刺激了约20%的CD4⁺细胞和30%的CD8⁺细胞增殖。加入抗ICAM-1抗体后，这些频率分别增加到30%和40%。抗CD3、抗CD4/CD8和抗LFA-1的组合获得了最大活化频率，该组合刺激约40%的单个CD4⁺细胞和至少60%的单个CD8⁺细胞进行细胞分裂。在这些条件下，30%-40%的所得CD4⁺克隆和超过90%的CD8⁺克隆分泌IL-3和干扰素-γ（IFN-γ）。除了比CD4⁺细胞以更高频率做出反应外，CD8⁺细胞形成了更大的克隆，产生的两种细胞因子水平高4倍。尽管在逆转录和聚合酶链反应扩增后的mRNA水平上，在CD4⁺和CD8⁺克隆中可以检测到IL-2、IL-3、IFN-γ、粒细胞-巨噬细胞集落刺激因子和肿瘤坏死因子α的表达，但在任何测试克隆中均未检测到IL-4或IL-6的分泌或mRNA表达。结论是通过LFA-1或ICAM-1对T细胞进行共刺激可以在没有辅助细胞的情况下增强T细胞受体依赖性活化，并且这种刺激模式导致表达有限范围的细胞因子基因。
