Haynes B F, Bunn P, Mann D, Thomas C, Eisenbarth G S, Minna J, Fauci A S
J Clin Invest. 1981 Feb;67(2):523-30. doi: 10.1172/JCI110062.
Using a panel of monoclonal antibodies and rabbit heteroantisera, we have studied the cell surface markers of peripheral blood (PB) Sezary cells from six patients with mycosis fungoides or Sezary syndrome, disease grouped within the spectrum of cutaneous T cell lymphomas (CTCL). Furthermore, we have studied two cell lines (Hut 78 and Hut 102) derived from malignant Sezary T cells from CTCL patients. The monoclonal antibody 3A1 defines a major human PB T cell subset (85% of PB T cells) while the antigen defined by the monoclonal antibody 4F2 is present on a subset (70%) of activated PB T cells and on circulating PB monocytes. In contrast to normal subjects in whom 60-70% of circulating PB mononuclear cells were 3A1(+) T cells, PB mononuclear cells from six CTCL patients studied had an average of only 10.6+/-3.2% 3A1(+) T cells. Whereas 85% of E-rosette positive cells from normal individuals were 3A1(+), virtually all E-rosette positive T cells from the Sezary patients were 3A1(-). Two patients with high numbers of circulating Sezary T cells had both aneuploid and diploid PB T cell populations present; after separation of PB T cells into 3A1(+) and 3A1(-) cell suspensions, all 3A1(-) cells were found to be aneuploid. In contrast to normal resting PB T cells which were 4F2(-), all PB Sezary cells were 4F2(+), suggesting a state of activation. The 3A1 antigen was on a variety of acute lymphoblastic leukemia T cell lines (HSB-2, RPMI-8402, MOLT4, CEM) but was absent on the Hut 78 and Hut 102 Sezary T cell lines. Using rabbit anti-human T and anti-human Ia (p23, 30) antisera, we found that all malignant Sezary PB cells tested were killed by anti-T cell antiserum plus complement but not by anti-Ia plus complement. In contrast, Sezary cell lines Hut 78 and 102, were killed by both anti-T cell antiserum and anti-Ia plus complement. Similar to 3A1(-) normal PB T cells, 3A1(-) Sezary PB T cells proliferated poorly to phytohemagglutinin and concanavalin A. However, 3A1(-) Sezary T cells were able to provide T cell help towards pokeweed mitogen-induced in vitro B cell immunoglobulin synthesis, an immunoregulatory function limited to 3A1(+) T cells in normal subjects.Thus, the 3A1 antigen is present on 85% of normal PB T cells, and on most T-acute lymphoblastic leukemia lines tested; in contrast the 3A1 antigen is not present on the majority of circulating malignant Sezary PB T cells nor on T cell lines derived from malignant Sezary T cells. The lack of expression of the 3A1 antigen may be associated with malignant transformation of T cells in CTCL and may be an important marker for tracing the clonal origin of the malignant Sezary T cell.
我们使用一组单克隆抗体和兔异种抗血清，研究了6例蕈样肉芽肿或Sezary综合征患者外周血（PB）Sezary细胞的细胞表面标志物，这两种疾病属于皮肤T细胞淋巴瘤（CTCL）范畴。此外，我们还研究了源自CTCL患者恶性Sezary T细胞的两条细胞系（Hut 78和Hut 102）。单克隆抗体3A1可识别主要的人类PB T细胞亚群（占PB T细胞的85%），而单克隆抗体4F2所识别的抗原存在于一部分（70%）活化的PB T细胞及循环PB单核细胞上。与正常受试者中60 - 70%的循环PB单核细胞为3A1(+) T细胞不同，所研究的6例CTCL患者的PB单核细胞平均仅有10.6±3.2%的3A1(+) T细胞。正常个体中85%的E花环阳性细胞为3A1(+)，而Sezary患者几乎所有的E花环阳性T细胞均为3A1(-)。两名循环Sezary T细胞数量较多的患者，其PB T细胞群体中既有非整倍体又有二倍体细胞；将PB T细胞分离为3A1(+)和3A1(-)细胞悬液后，发现所有3A1(-)细胞均为非整倍体。与正常静息PB T细胞为4F2(-)不同，所有PB Sezary细胞均为4F2(+)，提示处于活化状态。3A1抗原存在于多种急性淋巴细胞白血病T细胞系（HSB - 2、RPMI - 8402、MOLT4、CEM）上，但在Hut 78和Hut 102 Sezary T细胞系上不存在。使用兔抗人T和抗人Ia（p23、30）抗血清，我们发现所有检测的恶性Sezary PB细胞均被抗T细胞抗血清加补体杀伤，但不被抗Ia加补体杀伤。相比之下，Sezary细胞系Hut 78和102可被抗T细胞抗血清及抗Ia加补体杀伤。与3A1(-)正常PB T细胞相似，3A1(-) Sezary PB T细胞对植物血凝素和刀豆球蛋白A的增殖反应较差。然而，3A1(-) Sezary T细胞能够为商陆有丝分裂原诱导的体外B细胞免疫球蛋白合成提供T细胞辅助，这是一种在正常受试者中仅限于3A1(+) T细胞的免疫调节功能。因此，3A1抗原存在于85%的正常PB T细胞及大多数检测的T急性淋巴细胞白血病细胞系上；相反，3A1抗原不存在于大多数循环恶性Sezary PB T细胞及源自恶性Sezary T细胞的T细胞系上。3A1抗原表达的缺失可能与CTCL中T细胞的恶性转化有关，可能是追踪恶性Sezary T细胞克隆起源的重要标志物。
