Axelsson B, Youseffi-Etemad R, Hammarström S, Perlmann P
Department of Immunology, University of Stockholm, Sweden.
J Immunol. 1988 Nov 1;141(9):2912-7.
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.
CD43（大唾液酸糖蛋白）是一种高度糖基化的蛋白质，几乎在所有胸腺来源的淋巴细胞、B细胞亚群以及粒细胞上均有表达。最近研究发现，一种抗CD43单克隆抗体（L10）可诱导T细胞增殖，其效果与抗CD3抗体相当。据报道，L10抗体可与唾液酸化和去唾液酸化的CD43发生反应。为了进一步阐明CD43在各种T细胞功能中的作用，我们研究了另外两种针对CD43上唾液酸依赖性表位的单克隆抗体（B1B6和E11B，IgG1）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）会导致细胞迅速聚集。Fab片段也具有活性，不过所需浓度要高10倍。细胞聚集依赖于活跃的细胞代谢（叠氮化物和低温可抑制）、二价阳离子（Mg2+）的存在，并且可被抗CD18抗体抑制，但不能被抗CD11a抗体（白细胞功能相关抗原-1α）抑制。单独以可溶性形式将B1B6和E11B添加到外周血淋巴细胞（PBL）或T细胞中时，它们的促有丝分裂能力较弱。然而，用B1B6处理2天的PBL培养上清液含有白细胞介素-2（IL-2）活性。在此期间，CD25+细胞数量未见增加。外源性添加的IL-2在激活PBL时与B1B6或E11B不存在协同作用，而向IL-2内源性产生较低的激活系统（佛波酯或可溶性抗CD3）中添加这些抗体可显著增强增殖。抗CD43抗体可增强刀豆蛋白A（Con A）或菜豆白细胞凝集素诱导的T细胞增殖反应。F(ab')2片段比Fab片段能更显著地增强增殖，这表明CD43分子的交联是放大信号的一个基本特征。与单独用Con A激活的培养物相比，用B1B6-Con A激活的培养物中CD25+细胞和母细胞数量增加，IL-2产生也增加。结果表明，可通过CD43转导调节信号这些信号可能起到改变同型或异型T细胞黏附以及IL-2自分泌产生的作用。
