Cesano A, O'Connor R, Nowell P C, Lange B, Clark S C, Santoli D
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Blood. 1993 May 15;81(10):2714-22.
Bone marrow (BM) cells from a child with an immature (CD3-) acute T lymphoblastic leukemia (T-ALL) bearing no chromosomal abnormalities failed to grow in long-term culture in the presence or absence of recombinant human (rh) growth factors but could be engrafted in severe combined immunodeficient (SCID) mice and induced leukemia. The leukemic cells recovered from the animal tissues could be adapted to grow in vitro in the presence of rh interleukin-2 (IL-2) and give rise to a growth factor-dependent cell line designated TALL-107. This cell line expresses T-cell-specific mature markers (CD2, CD3/T-cell receptor [TCR] alpha beta, CD8, CD56), and its growth can be inhibited by IL-4 of all the cytokines tested. Similar to the original leukemic blasts, TALL-107 cells are clonal, have rearranged TCR-beta, gamma, and delta loci, and a normal 46 XY karyotype. However, unlike the patient's BM cells, the TALL-107 cell line displays potent tumoricidal activity that is not major histocompatibility complex restricted. The magnitude of mRNA expression of perforin and serine esterases and of lytic activity depends on the doses of IL-2 added. TALL-107 cells can also be triggered by CD3- and CD2-specific monoclonal antibodies (MoAbs) to mediate reverse tumor cell lysis. In addition, this cell line produces high levels of interferon gamma and tumor necrosis factor alpha on stimulation with anti-CD3 and/or anti-CD2 MoAb both in the presence or absence of IL-2. The overall data indicate that the SCID mouse is able to support the functional maturation and expansion of a cytotoxic T-cell subset from some types of T-ALL.
一名患有未成熟（CD3 -）急性T淋巴细胞白血病（T - ALL）且无染色体异常的儿童的骨髓（BM）细胞，在有或无重组人（rh）生长因子的情况下，均无法在长期培养中生长，但可植入严重联合免疫缺陷（SCID）小鼠体内并诱发白血病。从动物组织中回收的白血病细胞可在rh白细胞介素-2（IL - 2）存在的情况下适应体外生长，并产生一种依赖生长因子的细胞系，命名为TALL - 107。该细胞系表达T细胞特异性成熟标志物（CD2、CD3/T细胞受体[TCR]αβ、CD8、CD56），在所测试的所有细胞因子中，其生长可被IL - 4抑制。与原始白血病母细胞相似，TALL - 107细胞是克隆性的，TCR -β、γ和δ基因座发生了重排，核型为正常的46 XY。然而，与患者的BM细胞不同，TALL - 107细胞系显示出强大的杀瘤活性，且不受主要组织相容性复合体限制。穿孔素、丝氨酸酯酶的mRNA表达量及溶解活性的大小取决于所添加的IL - 2剂量。TALL - 107细胞也可被CD3和CD2特异性单克隆抗体（MoAbs）触发，介导反向肿瘤细胞裂解。此外，无论有无IL - 2，该细胞系在用抗CD3和/或抗CD2 MoAb刺激时都会产生高水平的干扰素γ和肿瘤坏死因子α。总体数据表明，SCID小鼠能够支持某些类型T - ALL中细胞毒性T细胞亚群的功能成熟和扩增。
