Valtieri M, Santoli D, Caracciolo D, Kreider B L, Altmann S W, Tweardy D J, Gemperlein I, Mavilio F, Lange B, Rovera G
J Immunol. 1987 Jun 1;138(11):4042-50.
A human leukemia cell line (TALL-101) was established from the bone marrow of a patient with an undifferentiated acute T cell leukemia using the conditioned medium (CM) of the human T cell leukemia virus (HTLV) II-transformed human cell line J-LB1. Immunofluorescence analysis on the original leukemic cells indicated the presence of T cell markers (Leu-1, Tdt, and T11); however, the established TALL-101 cell line expressed only antigens commonly present on progenitor cells, thymocytes, and myelomonocytic cells, but not on mature T cells. A high percentage of TALL-101 cells displayed the Tac antigen which was down-regulated upon incubation in the presence of recombinant human (rH) interleukin 2 (IL 2). Interferon (IFN)-gamma induced the appearance of class II histocompatibility leukocyte antigens (HLA) and of a T cell marker (3A1), and enhanced the expression of transferrin receptors on these cells. Further evidence for a T cell lineage of the TALL-101 cell line was provided by both chromosomic and genotypic analysis showing a translocation in chromosome 14 typical of T cell leukemias, and a rearrangement of the T-beta receptor locus. The growth-promoting activity in the J-LB1-CM was identified as granulocyte-macrophage colony stimulatory factor (GM-CSF), a growth factor which stimulates proliferation of normal myelomonocytic cells and other progenitor cells, but not known to have an effect on T cells. Dose response curves of [3H]thymidine incorporation and growth indicated that TALL-101 cells were sensitive to very low concentrations of rHGM-CSF, 5 ng/ml inducing maximal proliferation in chemically defined medium. The TALL-101 cell line is strictly GM-CSF-dependent for growth: upon depletion of GM-CSF from the culture medium, the cells stop proliferating immediately and die within 1 to 2 wk. The overall data, showing that GM-CSF is able to support the growth of a highly undifferentiated T cell leukemia, strongly suggests that this factor might have similar growth promoting effects on other immature T cell leukemias, and possibly, on normal T cell progenitors.
用人T细胞白血病病毒（HTLV）II转化的人细胞系J-LB1的条件培养基（CM），从一名未分化急性T细胞白血病患者的骨髓中建立了人白血病细胞系（TALL-101）。对原始白血病细胞的免疫荧光分析表明存在T细胞标志物（Leu-1、TdT和T11）；然而，建立的TALL-101细胞系仅表达祖细胞、胸腺细胞和骨髓单核细胞共有的抗原，而成熟T细胞不表达。高比例的TALL-101细胞显示Tac抗原，在重组人（rH）白细胞介素2（IL-2）存在下孵育时该抗原下调。干扰素（IFN）-γ诱导II类组织相容性白细胞抗原（HLA）和一种T细胞标志物（3A1）出现，并增强这些细胞上转铁蛋白受体的表达。染色体和基因型分析均显示14号染色体易位，这是T细胞白血病的典型特征，以及T-β受体基因座重排，为TALL-101细胞系的T细胞谱系提供了进一步证据。J-LB1-CM中的生长促进活性被鉴定为粒细胞-巨噬细胞集落刺激因子（GM-CSF），一种刺激正常骨髓单核细胞和其他祖细胞增殖的生长因子，但已知对T细胞无作用。[3H]胸腺嘧啶核苷掺入和生长的剂量反应曲线表明，TALL-101细胞对极低浓度的rHGM-CSF敏感，5 ng/ml在化学成分确定的培养基中诱导最大增殖。TALL-101细胞系的生长严格依赖GM-CSF：从培养基中耗尽GM-CSF后，细胞立即停止增殖并在1至2周内死亡。总体数据表明GM-CSF能够支持高度未分化的T细胞白血病的生长，强烈提示该因子可能对其他未成熟T细胞白血病以及可能对正常T细胞祖细胞具有类似的生长促进作用。
