Immunogenicity of bacterial carbohydrates: cholera toxin modulates the immune response against dextran B512
Immunogenicity of bacterial carbohydrates: cholera toxin modulates the immune response against dextran B512
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DOI：
10.1046/j.1365-2567.1997.00314.x
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发表时间：
1997-09-01
期刊：
影响因子：
6.4
通讯作者：
Fernandez, C
中科院分区：
文献类型：
--
作者：
Sverremark, E;Fernandez, C
天然葡聚糖 B512 是一种 T 细胞非依赖性 (TI) 抗原。通过将低分子量 (MW) 葡聚糖与蛋白质结合，可以获得针对葡聚糖的 T 细胞依赖性 (TD) 反应。我们之前报道过天然葡聚糖和两种不同的蛋白质-葡聚糖缀合物对免疫系统的影响。虽然一种类型的缀合物诱导了最佳 TD 反应，但另一种缀合物（“次优”）引起的反应与天然葡聚糖诱导的反应更相似，即几乎没有免疫球蛋白类别转换，并且具有与初级反应相似程度的次级反应。为了研究是否有可能增强抗葡聚糖反应，我们检查了霍乱毒素 (CT) 在我们的葡聚糖模型系统中的作用。 CT 是一种有效的粘膜佐剂以及全身佐剂，对 T 细胞、B 细胞和抗原呈递细胞有作用。我们证明 CT 对于 TD 和 TI 形式的右旋糖酐来说都是非常有效的佐剂。与传统的明矾佐剂相比，在给予 CT 和缀合物后，检测到 IgM 和 IgG 抗葡聚糖抗体的产生显着增加。对于次优 TD 缀合物，效果最为明显。 CT 还能够部分消除 TI 2 型 (TI-2) 无反应株 CBA/N 对葡聚糖的无反应性。 CT 还被发现是天然右旋糖酐的一种非常有效的佐剂，联合使用 CT 后次级 IgM 水平提高了八倍。此外，CTB-Dx 是 CT 无毒部分和低分子量、非免疫原性葡聚糖的缀合物，在裸鼠中引发抗葡聚糖反应。总的来说，我们的数据表明，通过联合给予 CT 可以提高 TD 和 TI 形式碳水化合物的免疫原性。这表明佐剂作用有两个组成部分，一个可以增强 T 细胞的抗原呈递和共刺激，另一个可以对 B 细胞产生直接刺激作用。
Native dextran B512 is a T-cell-independent (TI) antigen. By conjugating low molecular weight (MW) dextran to protein, a T-cell-dependent (TD) response against dextran can be obtained. We have previously reported the effects of native dextran and two different protein-dextran conjugates on the immune system. While one type of conjugate induced an optimal TD response, the other conjugate ('suboptimal') evoked a response more similar to that induced by native dextran, i.e. with little immunoglobulin class switch and with a secondary response of similar magnitude to the primary response. In order to investigate if it was possible to augment the anti-dextran response we examined the effects of cholera toxin (CT) in our dextran model system. CT is a potent mucosal, as well as systemic, adjuvant with effects on T cells, B cells and antigen-presenting cells. We show that CT is a very efficient adjuvant for both the TD and TI forms of dextran. A major increase in IgM and IgG anti-dextran antibody production was detected after administration of CT together with the conjugates compared with a conventional alum adjuvant. The effect was most pronounced for the suboptimal TD conjugate. CT was also able partially to abrogate the unresponsiveness to dextran in the TI type 2 (TI-2) non-responder strain CBA/N. CT was also found to be a very potent adjuvant for native dextran, secondary IgM levels were enhanced eightfold by the co-administration of CT. Furthermore CTB-Dx, which is a conjugate of the non-toxic part of CT and low MW, non-immunogenic dextran, elicited an anti-dextran response in nude mice. Collectively, our data show that it is possible to improve the immunogenicity of both TD and TI forms of a carbohydrate by co-administration of CT. This is indicative of two components of the adjuvant effect, one could enhance antigen presentation and costimulation of T cells and the other could have a direct stimulatory effect on B cells.