Induction of aggregation and enhancement of proliferation and IL-2 secretion in human T cells by antibodies to CD43.
Induction of aggregation and enhancement of proliferation and IL-2 secretion in human T cells by antibodies to CD43.
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CD43 抗体诱导人 T 细胞聚集并增强增殖和 IL-2 分泌。
DOI：
10.4049/jimmunol.141.9.2912
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发表时间：
1988
影响因子：
4.4
通讯作者：
P. Perlmann
中科院分区：
文献类型：
--
作者：
B. Axelsson;R. Youseffi;Sten Hammarström;P. Perlmann
CD 43（大唾液酸糖蛋白）是一种高度糖基化的蛋白质，在几乎所有胸腺来源的淋巴细胞、B细胞亚群和粒细胞上表达。最近，抗CD 43 mAb（L10）显示出诱导T细胞增殖的能力与抗CD 3相当。据报道，L10抗体与唾液酸化和去唾液酸化的CD 43反应。为了进一步阐明CD 43在各种T细胞功能中的作用，我们研究了针对CD 43上唾液酸依赖性表位的另外两种mAb（B1 B6和E11 B，IgG 1）的生物学特性。向新鲜分离的T细胞或T细胞系中加入少量抗体（5至10 ng/ml）导致细胞快速聚集。Fab片段也有活性，尽管浓度高10倍。聚集依赖于活性细胞代谢（受叠氮化物和低温抑制）、二价阳离子（Mg 2+）的存在，并受CD 18抗体抑制，但不受CD 11 a（白细胞功能相关Ag-1 α）抗体抑制。B1 B6和E11 B单独以可溶性形式加入PBL或T细胞时，促有丝分裂性较差。而B1 B6处理2天的PBL培养上清则含有IL-2活性。在同一时期，未观察到CD 25+细胞数量增加。外源性添加的IL-2在PBL的活化中不与B1 B6或E11 B协同，而通过将抗体添加到具有低内源性IL-2产生的活化系统（PMA或可溶性抗CD 3）中，增殖显著增加。抗CD 43抗体增强了由ConA或来自菜豆的白细胞凝集素诱导的T细胞增殖反应。F（ab '）2片段比Fab片段显著更好地增强增殖，表明CD 43分子的交联是扩增信号的基本特征。与单独ConA激活的培养物相比，在B1 B6-ConA激活的培养物中观察到CD 25+细胞和母细胞数量增加以及IL-2产生增加。结果表明，调节信号，这可能会改变同型或异型T细胞粘附以及自分泌产生的IL-2，可以通过CD 43转导。
CD43 (large sialoglycoprotein) is a heavily glycosylated protein expressed on virtually all thymus-derived lymphocytes, on a subpopulation of B cells and on granulocytes. Recently, an anti-CD43 mAb (L10) was shown to induce proliferation in T cells comparable to that induced by anti-CD3. The L10 antibody was reported to react with both sialylated and desialylated CD43. In order to further elucidate the role of CD43 in various T cell functions we have studied the biologic properties of two other mAb (B1B6 and E11B, IgG1) directed against sialic acid-dependent epitopes on CD43. Addition of low amounts of antibody (5 to 10 ng/ml) to freshly isolated T cells or to T cell lines resulted in a rapid clustering of the cells. Fab fragments were also active albeit at a 10-fold higher concentration. Aggregation was dependent on active cell metabolism (inhibited by azide and at low temperatures), on the presence of divalent cations (Mg2+) and was inhibited by antibodies to CD18 but not by antibodies to CD11a (leukocyte function-associated Ag-1 alpha). B1B6 and E11B were poorly mitogenic when added alone in soluble form to PBL or to T cells. However, supernatants from cultures of PBL treated with B1B6 for 2 days contained IL-2 activity. No increase in the number of CD25+ cells was seen during the same period. Exogenously added IL-2 did not synergize with B1B6 or E11B in activation of PBL, whereas proliferation was significantly increased by the addition of the antibodies to activation systems with low endogenous production of IL-2 (PMA or soluble anti-CD3). The anti-CD43 antibodies amplified T cell proliferative responses induced by Con A or leukoagglutinin from Phaseolus vulgaris. F(ab')2 fragments enhanced proliferation significantly better than Fab fragments suggesting that cross-linking of CD43 molecules was an essential features of the amplifying signal. Compared with cultures activated by Con A alone, an increased number of CD25+ cells and of blast cells as well as an increased IL-2 production was observed in cultures activated by B1B6-Con A. The results indicate that regulatory signals, which may function to modify homo- or heterotypic T cell adhesion as well as autocrine production of IL-2, can be transduced through CD43.