Arce Sergio, Nawar Hesham F, Russell Michael W, Connell Terry D
Department of Microbiology and Immunology, The University of Buffalo, State University of New York at Buffalo, 138 Farber Hall, 3435 Main St., Buffalo, NY 12214, USA.
Infect Immun. 2005 May;73(5):2718-27. doi: 10.1128/IAI.73.5.2718-2727.2005.
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(T14I), 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.
霍乱毒素（CT）、LT-IIa和LT-IIb是强效佐剂，可诱导不同的辅助性T（Th）细胞细胞因子谱以及免疫球蛋白G（IgG）亚类和IgA抗体反应。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由肠毒素与其同源神经节苷脂受体的结合所引发，评估了与这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反应的影响。LT-IIa、LT-IIb和CT与几种淋巴细胞群体的结合模式对每种肠毒素而言都是独特的。LT-IIa和CT可诱导CD8(+) T细胞凋亡，但LT-IIb不能。LT-IIa(T34I)是一种与神经节苷脂无可检测结合的突变体，不会诱导凋亡。LT-IIa(T14I)是一种仅与GM(1)结合但不诱导凋亡的突变体，它对CD8(+) T细胞表面GM(1)的阻断并未抑制LT-IIa诱导的凋亡。用CT处理可消除丝裂原诱导的CD8(+) T细胞增殖，而对LT-IIa诱导的凋亡敏感的静息CD8(+) T细胞在丝裂原激活后对凋亡的抗性增强。暴露于CT而非LT-IIa或LT-IIb可抑制丝裂原驱动的CD4(+) T细胞增殖以及CD25和CD69的表达。在丝裂原刺激的B细胞中，CT而非LT-IIa或LT-IIb可增强CD86的表达水平，而只有CT可诱导B细胞分化为浆细胞。因此，LT-IIa、LT-IIb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。
