Sprent J, Schaefer M, Gao E K, Korngold R
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
J Exp Med. 1988 Feb 1;167(2):556-69. doi: 10.1084/jem.167.2.556.
Detailed information was sought on the capacity of purified Lyt-2+ cells to mediate lethal graft-versus-host disease (GVHD) directed to class I H-2 differences. When B6 Lyt-2+ cells were transferred to irradiated class I-different (B6 x bm 1)F1 mice, three different patterns of lethal GVHD were observed. First, rapid death from hematopoietic failure occurred when Lyt-2+ cells were transferred together with host-type marrow cells; this form of GVHD probably reflected direct destruction of stem cells by Lyt-2+ cytotoxic cells. Second, a pattern of late-onset, chronic GVHD resulting in death only after 4-6 wk occurred when Lyt-2+ cells were supplemented with donor marrow. This syndrome developed in the apparent absence of L3T4+ cells and was observed with either high or low doses of Lyt-2+ cells and with either light or heavy irradiation of the host. Third, an acute form of GVHD resulted when Lyt-2+ cells plus donor marrow cells were supplemented with exogenous help, i.e., by adding small doses of donor L3T4+ cells or injecting the hosts with rIL-2. Although L3T4+ cells potentiated GVHD when injected in small doses, supplementing Lyt-2+ cells with large doses of L3T4+ cells paradoxically led to marked protection; symptoms of GVHD were mild and no deaths occurred.
我们研究了纯化的Lyt-2⁺细胞介导针对I类H-2差异的致死性移植物抗宿主病（GVHD）的能力。当将B6 Lyt-2⁺细胞转移至经照射的I类不同（B6×bm1）F1小鼠时，观察到三种不同模式的致死性GVHD。首先，当Lyt-2⁺细胞与宿主型骨髓细胞一起转移时，会因造血功能衰竭而迅速死亡；这种形式的GVHD可能反映了Lyt-2⁺细胞毒性细胞对干细胞的直接破坏。其次，当Lyt-2⁺细胞补充有供体骨髓时，会出现一种迟发性慢性GVHD模式，仅在4-6周后导致死亡。这种综合征在明显缺乏L3T4⁺细胞的情况下发生，并且在高剂量或低剂量的Lyt-2⁺细胞以及宿主接受轻度或重度照射时均观察到。第三，当Lyt-2⁺细胞加供体骨髓细胞补充外源性辅助，即添加小剂量供体L3T4⁺细胞或给宿主注射rIL-2时，会导致急性GVHD形式。尽管小剂量注射L3T4⁺细胞可增强GVHD，但用大剂量L3T4⁺细胞补充Lyt-2⁺细胞却反常地导致明显的保护作用；GVHD症状轻微且无死亡发生。
