Kumar V, Luevano E, Bennett M
J Exp Med. 1979 Sep 19;150(3):531-47. doi: 10.1084/jem.150.3.531.
Natural killer (NK) cells from nonimmunized mice capable of lysing EL-4 (C57BL/6 strain H-2b) tissue culture-adapted lymphoma cells have been analyzed and compared with NK cells which lyse YAC-1 (A-strain, H-2a) lymphoma cells. A correlation was seen in the ability of inbred and B6D2F1 mice to reject C57BL/6 (B6) bone-marrow grafts and the ability of their spleen cells to lyse EL-4 cells in vitro. This suggests that hybrid or hemopoietic histocompatibility antigens, (Hh-1b), relevant in the rejection of B6 stem cells may also be the relevant target structures for the anti-EL-4 NK cells. Certain features of these NK cells are similar to the NK cells reactive against YAC-1 cells. Both types of NK cells are present in athymic nude mice, are not affected by treatment with anti-immunoglobulin plus complement, and are not depleted by techniques that remove macrophages. NK activity against both targets is stimulated 3 d after injection of Corynebacterium parvum, and 24 h after challenge with polyinosinic:polycytidylic acid. Hydrocortisone acetate and cyclophosphamide lead to reduction of NK activity within 2-3 d after administration. However, the anti-YAC and anti-EL-4 NK reactivities differed in several important respects. Treatment of mice with 89Sr, the bone-seeking isotope, to deplete marrow-dependent cells, depleted the anti-YAC-1 but not anti-EL-4 cell functions. Anti-EL-4 NK cells were unaffected by silica particles in vivo or in vitro; the NK cells reactive to EL-4 cells matured functionally much earlier in life (5 d of age) and the function did not decline with age. Irradiated mice reconstituted with syngeneic marrow or spleen cells developed functional NK cells against EL-4 targets before they developed anti-YAC-1 NK cells in their spleen. Thus anti-EL-4 NK cells that express hybrid resistance in vitro appear to differ from anti-YAC-1 NK cells and do not require an intact marrow microenvironment for functional differentiation. Despite differences in the NK-cell types involved in the lysis of YAC-1 and EL-4 cells, these two tumor cells share certain common determinants. This was ascertained both by cold competition and by utilization of YAC-1 and EL-4 cell monolayers as immunoadsorbents. We conclude that Hh-1b is the common antigen present in EL-4 and YAC-1 cells, because B6D2F1 anti-B6 (anti-Hh-1b) cytotoxic T lymphocytes lysed both the tumor cells. Our data suggest that Hh-1b antigen is recognized by both types of NK cells, but that additional determinants must be present on YAC-1 cells. Two models of NK cell lysis compatible with the data are presented.
对来自未免疫小鼠、能够裂解EL-4（C57BL/6品系，H-2b）组织培养适应型淋巴瘤细胞的自然杀伤（NK）细胞进行了分析，并与能够裂解YAC-1（A品系，H-2a）淋巴瘤细胞的NK细胞进行了比较。在近交系小鼠和B6D2F1小鼠排斥C57BL/6（B6）骨髓移植的能力与其脾细胞在体外裂解EL-4细胞的能力之间发现了相关性。这表明，与B6干细胞排斥相关的杂种或造血组织相容性抗原（Hh-1b）也可能是抗EL-4 NK细胞的相关靶结构。这些NK细胞的某些特征与针对YAC-1细胞的反应性NK细胞相似。两种类型的NK细胞都存在于无胸腺裸鼠中，不受抗免疫球蛋白加补体处理的影响，也不会因去除巨噬细胞的技术而耗竭。注射微小棒状杆菌3天后以及用聚肌苷酸:聚胞苷酸攻击24小时后，针对两种靶标的NK活性均受到刺激。醋酸氢化可的松和环磷酰胺在给药后2 - 3天内导致NK活性降低。然而，抗YAC和抗EL-4 NK反应性在几个重要方面有所不同。用亲骨性同位素89Sr处理小鼠以耗尽骨髓依赖性细胞，可耗尽抗YAC-1但不影响抗EL-4细胞功能。抗EL-4 NK细胞在体内或体外均不受二氧化硅颗粒的影响；对EL-4细胞有反应的NK细胞在生命早期（5日龄）功能成熟得更早，且其功能不会随年龄下降。用同基因骨髓或脾细胞重建的受辐照小鼠在其脾脏中产生针对EL-4靶标的功能性NK细胞之前，先产生了针对YAC-1的NK细胞。因此，在体外表现出杂种抗性的抗EL-4 NK细胞似乎与抗YAC-1 NK细胞不同，并且其功能分化不需要完整的骨髓微环境。尽管参与裂解YAC-1和EL-4细胞的NK细胞类型存在差异，但这两种肿瘤细胞具有某些共同的决定簇。这通过冷竞争以及利用YAC-1和EL-4细胞单层作为免疫吸附剂得以确定。我们得出结论，Hh-1b是EL-4和YAC-1细胞中存在的共同抗原，因为B6D2F1抗B6（抗Hh-1b）细胞毒性T淋巴细胞可裂解这两种肿瘤细胞。我们的数据表明，两种类型的NK细胞都能识别Hh-1b抗原，但YAC-1细胞上必定还存在其他决定簇。本文提出了两个与数据相符的NK细胞裂解模型。
