Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.
Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.
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人类胸腺依赖性膜抗原：TH2 抗原单克隆抗体抑制细胞介导的淋巴溶解。
DOI：
10.1073/pnas.78.1.544
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发表时间：
1981
影响因子：
11.1
通讯作者：
R. Good
中科院分区：
文献类型：
--
作者：
R. Evans;D. Wall;C. Platsoucas;F. Siegal;S. Fikrig;C. Testa;R. Good
在先前的研究中，一种称为T（H2）的表面膜组分的异源抗血清被用于定义人T细胞的两个亚群（T（H2）（+）和T（H2）（-）），发现它们在体外表达不同的活性组。在本研究中，我们制备了单克隆抗体的表面决定簇，仅限于属于这两个子集的T细胞。被称为alphaLeu-2a和alphaLeu-2b的两种抗体似乎定义了由原始T（H2）抗血清鉴定的相同表面抗原，与外周血中57-84%的胸腺细胞和22-46%的红细胞玫瑰花结形成细胞（ERF-C）反应。另外两种单克隆抗体，称为alphaLeu-3a和alphaLeu-3b，与相同的胸腺细胞亚群（78-89%）和外周血ERF-C（47-78%）反应，但与alphaLeu-2a和alphaLeu-2b不同，不表现出交叉阻断;即，用α Leu-3a标记细胞不抑制随后的α Leu-3b结合。与alphaLeu-2a反应的T细胞显示与alphaLeu-3a不反应，表明由此定义了两个单独的T细胞亚群，Leu-2（以前的T（H2）（+））和Leu-3（T（H2）（-））T细胞。这两个T细胞亚群组成了ERF-C亚群（80-95%），先前由T细胞膜抗原（Leu-1）的单克隆抗体定义，该抗原在正常淋巴细胞上具有胸腺依赖性分布，但由一些表面免疫球蛋白阳性（sIg（+））白血病淋巴细胞表达。本文报道的Leu抗体均不与sIg（+）、Leu-1（+）白血病细胞反应，也不与具有B细胞特征性表面标记的正常造血细胞或淋巴细胞反应。在不存在补体的情况下进行Leu抗体对效应T细胞在细胞介导的淋巴溶解中的杀伤的阻断作用的研究。这些实验确定了以下几点：（i）alphaLeu-2a消除了细胞毒性T细胞对同种异体植物血凝素刺激的原始细胞的杀伤作用，（ii）alphaLeu-2b对杀伤作用的抑制明显小于alphaLeu-2a的抑制作用，以及（iii）其他抗体，包括alphaLeu-1、alphaLeu-3a和alphaLeu-3b，对细胞介导的淋巴细胞溶解中的杀伤作用几乎没有或没有影响。这些研究结果的相关性进行了讨论，以前的研究在小鼠和人。
In prior studies a heteroantiserum to a surface membrane component termed T(H2) was used to define two subsets of human T cells (T(H2) (+) and T(H2) (-)), which were found to express distinct sets of activities in vitro. In the present studies we prepared monoclonal antibodies to surface determinants that are restricted to T cells belonging to each of these two subsets. Two antibodies, termed alphaLeu-2a and alphaLeu-2b, which seem to define the same surface antigen identified by the original T(H2) antiserum, reacted with 57-84% of thymocytes and 22-46% of the erythrocyte-rosette-forming cells (ERF-C) in peripheral blood. Two other monoclonal antibodies, termed alphaLeu-3a and alphaLeu-3b, reacted with the same subpopulation of thymocytes (78-89%) and peripheral blood ERF-C (47-78%) but, unlike alphaLeu-2a and alphaLeu-2b, did not exhibit cross-blocking; i.e., labeling cells with alphaLeu-3a did not inhibit the subsequent binding of alphaLeu-3b. T cells reactive with alphaLeu-2a were shown to be unreactive with alphaLeu-3a, indicating that two separate subpopulations of T cells, Leu-2 (formerly T(H2) (+)) and Leu-3 (T(H2) (-)) T cells, were thereby defined. These two T cell subsets make up the subpopulation of ERF-C (80-95%) previously defined by a monoclonal antibody to a T cell membrane antigen (Leu-1) that has a thymus-dependent distribution on normal lymphocytes but is expressed by some surface-immunoglobulin-positive (sIg(+)) leukemic lymphocytes. None of the Leu antibodies reported here reacted with sIg(+), Leu-1(+) leukemic cells, nor did they react with normal hematopoietic cells or lymphoid cells that had surface markers characteristic of B cells. Studies of the blocking effects of Leu antibodies on killing in cell-mediated lympholysis by effector T cells were carried out in the absence of complement. These experiments established the following points: (i) alphaLeu-2a abolished the killing by cytotoxic T cells of allogeneic phytohemagglutinin-stimulated blasts, (ii) inhibition of killing by alphaLeu-2b was markedly less than inhibition by alphaLeu-2a, and (iii) other antibodies, including alphaLeu-1, alphaLeu-3a, and alphaLeu-3b, had little or no effect on killing in cell-mediated lympholysis. The relevance of these findings to prior studies done in the mouse and in man are discussed.