Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells
Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells
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DOI：
10.1128/iai.73.5.2718-2727.2005
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Connell, TD
中科院分区：
文献类型：
--
作者：
Arce, S;Nawar, HF;Connell, TD
霍乱毒素（CT）、LT-IIa和LT-IIb是诱导不同的T辅助（Th）细胞细胞因子谱和免疫球蛋白G（IgG）亚类和伊加抗体应答的有效佐剂。为了确定观察到的LT-IIa、LT-IIb和CT的不同免疫调节作用是否是由肠毒素与其同源神经节苷脂受体结合引起的，评价了与三种肠毒素相互作用的淋巴细胞谱系及其对体外各种淋巴细胞应答的影响。LT-IIa，LT-IIb和CT的几个淋巴细胞群体的结合模式是独特的每种肠毒素。LT-Ⅱ a和CT可诱导CD 8（+）T细胞凋亡，而LT-Ⅱ b无此作用。LT-IIa（T34 I），一个突变体，没有检测到结合神经节苷脂，不诱导细胞凋亡。LT-IIa（T141）是一种仅与GM（1）结合但不诱导凋亡的突变体，它对CD 8（+）T细胞表面GM（1）的阻断作用并不抑制LT-IIa诱导的凋亡。丝裂原诱导的CD 8（+）T细胞增殖被CT处理所消除，而对LT-IIa诱导的凋亡敏感的静息CD 8（+）T细胞在丝裂原激活后变得对凋亡更抵抗。暴露于CT，而不是LT-IIa或LT-IIb，抑制有丝分裂原驱动的CD 4（+）T细胞增殖和CD 25和CD 69的表达。在丝裂原刺激的B细胞中，CT而不是LT-IIa或LT-II B，增强CD 86的表达水平，而只有CT诱导B细胞分化为浆细胞。因此，LT-Ⅱ a，LT-Ⅱ b和CT表现出可区分的免疫调节特性，这可能取决于它们识别淋巴细胞上不同神经节苷脂受体的能力。
Cholera toxin (CT), LT-IIa, and LT-IIb are potent adjuvants which induce distinct T-helper (Th)-cell cytokine profiles and immunoglobulin G (IgG) subclass and IgA antibody responses. To determine if the distinct immune regulatory effects observed for LT-IIa, LT-IIb, and CT are elicited by binding of the enterotoxins to their cognate ganglioside receptors, the lineages of lymphoid cells that interact with the three enterotoxins and their effects on various lymphocyte responses in vitro were evaluated. Binding patterns of LT-IIa, LT-IIb, and CT to several lymphoid cell populations were distinctive for each enterotoxin. LT-IIa and CT, but not LT-IIb, induced apoptosis in CD8(+) T cells. LT-IIa(T34I), a mutant with no detectable binding to gangliosides, did not induce apoptosis. Blockade of GM(1), on the surface of CD8(+) T cells by LT-IIa(T141), a mutant that binds only to GM(1) but does not induce apoptosis, did not inhibit induction of apoptosis by LT-IIa. Mitogen-induced proliferation of CD8(+) T cells was abrogated by treatment with CT, while resting CD8(+) T cells which were sensitive to LT-IIa-induced apoptosis became more resistant to apoptosis after mitogen activation. Exposure to CT, but not to LT-IIa or LT-IIb, inhibited mitogen-driven CD4(+) T-cell proliferation and expression of CD25 and CD69. In mitogen-stimulated B cells, CT, but not LT-IIa or LT-IIb, enhanced expression levels of CD86, while only CT induced B-cell differentiation into plasma cells. Thus, LT-IIa, LT-IIb, and CT exhibit distinguishable immunomodulatory properties which are likely dependent upon their capacities to recognize different ganglioside receptors on lymphocytes.