Immunosuppressive factors produced by adult T cell leukemia (ATL) cells and its relation to ATL induction

成人T细胞白血病（Adult T cell leukemia， ATL）是一种由HTLV-i引起的独特的T细胞恶性肿瘤，ATL患者具有严重的免疫缺陷。我们研究了ATL患者免疫缺陷的机制和ATL细胞产生的免疫抑制因子的特性。ATL患者血清和ATL细胞或ATL细胞系培养上清可抑制T细胞分裂原诱导的正常外周血T细胞增殖反应。这种来源于ATL细胞的免疫抑制因子也直接作用于正常B细胞，抑制B细胞丝裂原诱导的B细胞增殖和向产igg细胞分化。然而，免疫抑制因子不影响正常巨噬细胞/单核细胞的抗原呈递和IL - 1的产生。htlv - i携带者血清和外周血淋巴细胞培养上质均未检测到免疫抑制活性。此外，这些因子还能抑制正常T细胞上CD3和CD4的组成性表达。采用Sephacryl S-200柱层析，分离出分子量为5万~ 7万道尔顿的单峰，采用色谱聚焦技术，等电点为4.2。抑菌活性对酸性处理不稳定，对碱、热、冻融和胰蛋白酶处理稳定。我们正在利用分子生物学技术进一步研究抑制因子的理化特性。这些结果提示ATL患者免疫缺陷状态是由ATL细胞产生的免疫抑制因子引起的。免疫缺陷状态不仅导致宿主的各种感染，也为白血病细胞和白血病发生ATL细胞的生长提供了更适宜的环境。

Adult T cell leukemia (ATL) is a unique T cell malignancy which is caused by HTLV-i and ATL patients possess severe immunodeficiency. We studied the mechanism of immunodeficiency in ATL patients and character of immunosuppressive factors produced by ATL cells. Sera from ATL patients and the culture supernatant from ATL cells or ATL cell lines suppressed the normal peripheral T cell proliferative responses induced by T cell mitogens. This immunosuppressive factors derived from ATL cells also acted on normal B cells directly and inhibited the proliferation and the differentiation into Ig-producing cells of B cells induced with B cell mitogen. However, the immunosuppressive factors did not affect on the antigen-presentation and IL 1-production of normal macrophages/monocytes. We could not detect the immunosuppressive activity from the sera and the culture suprenatant from peripheral lymphocytes of HTLV-I-carriers. Futhermore, the constitutive expression of CD3 and CD4 on normal T cells was inhibited by the factors. By Sephacryl S-200 column chromatography, the factors were fractionated as a single peak with the molecular weights of 50,000 to 70,000 daltons and their isoelectric point was 4.2 by chromatofocussing techniques. The suppressive activity was unstable to acidtreatment but stable to the treatment woth base, heat, freezing-thawing and trypsin. We are futher studying physiochemical characterization of the suppressive factors by the molecular biological techniques. From these results it can be suggested that the immunodeficiency state in ATL patients is caused by the immunosuppressive factors produced by ATL cells. The immunodeficiency state not only results in various kinds of infections in the host but also provides a more suitable environment for the growth of leukemia cells and leukemogenesis ATL cells.