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一种新的细胞表面抗原(T305),在急性白血病细胞和自身免疫疾病状态下出现频率增加。

A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states.

作者信息

Fox R I, Hueniken M, Fong S, Behar S, Royston I, Singhal S K, Thompson L

出版信息

J Immunol. 1983 Aug;131(2):762-7.

PMID:6602845
Abstract

Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.

摘要

通过用源自T-ALL的细胞系RPMI-8402免疫小鼠制备的单克隆抗体T305,能免疫沉淀一种单链糖蛋白,其分子量在还原条件下为160,000道尔顿,在非还原条件下为180,000道尔顿。在免疫荧光测定中,抗体T305与正常血液(22±6%)、胸腺(28±11%)和淋巴结(24±6%)中的一部分T细胞发生反应。在传染性单核细胞增多症患者的外周血(大于80%)、骨髓移植后的移植物抗宿主病(65±11%)、获得性免疫缺陷综合征(53±12%)中,发现与抗体T305反应的T细胞频率增加。与类风湿性关节炎患者外周血(18±7%)相比,其滑液中的T细胞与抗体T305反应的细胞频率增加(59±8%)。双色免疫荧光研究表明,在正常人和疾病状态的血液中,T305+T细胞主要与抗体Leu 2a(抑制/细胞毒性亚群)共染色。在进行细胞分选以获得T305+和T305-亚群后,我们证明:a)正常血液中的自然杀伤和抗体依赖性细胞毒性活性存在于T305+而非T305-T细胞中;b)混合淋巴细胞反应诱导的细胞毒性T细胞主要是T305+;c)T305-T细胞可在体外被有丝分裂原或同种异体B细胞诱导表达T305抗原;d)正常血液中T305+和T305-T细胞的DNA含量相似(超过95%的细胞处于G0/G1期);e)有丝分裂原刺激后,先前T305-细胞上T305抗原的诱导发生在S期之前;f)有丝分裂原刺激后,原来的T305-细胞比原来的T305+细胞掺入的[3H]-胸腺嘧啶显著更多(p小于0.001)。T305抗原不仅限于T细胞,因为它也存在于骨髓中的髓系前体细胞上,但不存在于多形核白细胞、红细胞、血小板、肌肉、肝脏、皮肤、肾脏、肺或大脑中。在25例急性白血病(6例T-ALL, 10/11例cALL, 7例AML, 1例AMOL)中的24例中发现了抗体T305,但在18例慢性白血病(B-CLL、T-CLL、null CLL、CML)中未发现。T305抗原的重要性在于它存在于某些自身免疫性疾病的大量T细胞上以及几乎所有急性白血病细胞上。它在未成熟和体外活化细胞上的分布表明它可能代表与细胞复制或分化相关信号的受体。

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