Boyer M W, Orchard P J, Gorden K B, Anderson P M, Mclvor R S, Blazar B R
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis 55455, USA.
Blood. 1995 May 1;85(9):2498-506.
The immune response to a murine myeloid leukemia (cell line C1498) was studied in vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function antigen-1 (LFA-1) on effectors and intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target cells. However, the ability of nonimmunized mice to resist an in vivo challenge of a low dose (10(4)) of C1498 was NK-cell, but not T-cell dependent. The failure of T cells to participate in the immune surveillance of a low leukemia burden appeared, in part, because of a lack of expansion of leukemia reactive CTL precursors (CTLp). Leukemia reactive CTLp frequency estimations in naive and leukemia bearing mice were not significantly different (range, 1:20,600 to 1:74,000) in contrast to immunized mice (range, 1:1,400 to 1:4,400). Leukemia reactive CTLp could be expanded to a level that could apparently mediate in vivo immune surveillance of 10(5) leukemia cells by injection of irradiated leukemia cells intraperitoneally (IP) or subcutaneously (SC), but not intravenously (IV). However, IV injection of 10(5) live leukemia cells engineered to secrete interleukin-2 (IL-2) resulted in systemic immunity mediated primarily by CD8+ T cells. We conclude that NK cells can mediate immune surveillance of a low leukemia burden. CD8+ CTL-mediated immune surveillance can eliminate a higher leukemia burden than NK cells, but requires T-cell help, which can be delivered by local IL-2. Both NK and CTL-mediated immune surveillance of C1498 murine myeloid leukemia is dependent on recognition through the LFA-1:ICAM adhesion pathway.
对小鼠髓系白血病（细胞系C1498）的免疫反应进行了体内和体外研究。结果表明，自然杀伤（NK）细胞和CD8 + 细胞毒性T淋巴细胞（CTL）在体外通过效应细胞上的白细胞功能抗原-1（LFA-1）与C1498靶细胞上的细胞间黏附分子-1（ICAM-1）和ICAM-2结合来裂解C1498。然而，未免疫小鼠抵抗低剂量（10⁴）C1498体内攻击的能力依赖于NK细胞，而非T细胞。T细胞未能参与低白血病负荷的免疫监视，部分原因是缺乏白血病反应性CTL前体（CTLp）的扩增。与免疫小鼠（范围为1:1400至1:4400）相比，未免疫小鼠和荷白血病小鼠中白血病反应性CTLp频率估计值无显著差异（范围为1:20600至1:74000）。通过腹腔内（IP）或皮下（SC）注射经辐射的白血病细胞，白血病反应性CTLp可扩增至显然能介导对10⁵个白血病细胞进行体内免疫监视的水平，但静脉内（IV）注射则不行。然而，静脉注射经基因工程改造以分泌白细胞介素-2（IL-2）的10⁵个活白血病细胞可导致主要由CD8 + T细胞介导的全身免疫。我们得出结论，NK细胞可介导对低白血病负荷的免疫监视。CD8 + CTL介导的免疫监视比NK细胞能消除更高的白血病负荷，但需要T细胞的帮助，而局部IL-2可提供这种帮助。NK和CTL介导的对C1498小鼠髓系白血病的免疫监视均依赖于通过LFA-1:ICAM黏附途径的识别。
