Sverremark E, Fernandez C
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Immunology. 1997 Sep;92(1):153-9. doi: 10.1046/j.1365-2567.1997.00314.x.
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.
天然右旋糖酐B512是一种非T细胞依赖性（TI）抗原。通过将低分子量（MW）右旋糖酐与蛋白质偶联，可以获得针对右旋糖酐的T细胞依赖性（TD）反应。我们之前报道过天然右旋糖酐和两种不同的蛋白质 - 右旋糖酐偶联物对免疫系统的影响。一种偶联物诱导出最佳的TD反应，而另一种偶联物（“次优”）引发的反应更类似于天然右旋糖酐诱导的反应，即免疫球蛋白类别转换很少，二次反应的幅度与初次反应相似。为了研究是否有可能增强抗右旋糖酐反应，我们在右旋糖酐模型系统中研究了霍乱毒素（CT）的作用。CT是一种有效的黏膜和全身佐剂，对T细胞、B细胞和抗原呈递细胞均有作用。我们发现CT对于TD和TI形式的右旋糖酐都是非常有效的佐剂。与传统的明矾佐剂相比，将CT与偶联物一起给药后，检测到IgM和IgG抗右旋糖酐抗体产生大幅增加。这种效果在次优TD偶联物中最为明显。CT还能够部分消除TI 2型（TI - 2）无反应品系CBA / N对右旋糖酐的无反应性。还发现CT对于天然右旋糖酐也是一种非常有效的佐剂，CT与天然右旋糖酐共同给药可使二次IgM水平提高八倍。此外，CTB - Dx是CT的无毒部分与低MW、无免疫原性的右旋糖酐的偶联物，可在裸鼠中引发抗右旋糖酐反应。总体而言，我们的数据表明，通过CT共同给药可以提高碳水化合物的TD和TI形式的免疫原性。这表明佐剂效应有两个组成部分，一个可以增强抗原呈递和T细胞的共刺激，另一个可以对B细胞有直接刺激作用。
