Cholera toxin and its B subunit promote dendritic cell vaccination with different influences on Th1 and Th2 development
Cholera toxin and its B subunit promote dendritic cell vaccination with different influences on Th1 and Th2 development
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DOI：
10.1128/iai.71.4.1740-1747.2003
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发表时间：
2003-04-01
影响因子：
3.1
通讯作者：
Holmgren, J
中科院分区：
文献类型：
--
作者：
Eriksson, K;Fredriksson, M;Holmgren, J
霍乱毒素(CT)是共递送抗原的强大粘膜佐剂，而其无毒B亚单位(CTB)是一种有效的粘膜载体分子，可产生对结合抗原的免疫应答。我们研究了CT和CTB对小鼠静脉注射体外处理的抗原冲击的树突状细胞(DC)免疫原性的影响。输注前，用游离卵白蛋白(OVA)、OVA与CT或CTB混合或OVA与CT和CTB的化学结合物(OVA-CT和OVA-CTB)冲击DC 90min。OVA冲击DC或OVA+CTB冲击DC可产生适度的抗体和T细胞反应。OVA与CTB的结合增强了随后的B细胞和T细胞对OVA的反应，并优先诱导Th2反应。CT在DC和OVA联合给药时是一种强佐剂，在与OVA-CTB联合给药并为Th1-Th2混合反应做好准备时甚至更强。如果将OVA与CT偶联，则抗体和T细胞反应进一步增强，这意味着CT可以利用结合抗原的载体和佐剂功能来进行DC疫苗接种。CT和CTB结合抗原的免疫增强能力与DC表面IL-1β的分泌上调和DC表面CD80和CD86的表达增加有关。这些结果表明，CT和CTB可以显著增强和部分引导DC疫苗诱导的针对Th1和Th2的免疫应答，这对DC疫苗的开发具有明显的意义。
Cholera toxin (CT) is a strong mucosal adjuvant for codelivered antigens, whereas its nontoxic B subunit (CTB) is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens. We investigated the effects of CT and CTB on the immunogenicity of in vitro-treated antigen-pulsed dendritic cells (DC) following intravenous injection into mice. Prior to infusion, DC were pulsed for 90 min with either free ovalbumin (OVA), OVA mixed with CT or CTB, or chemical conjugates of OVA with CT and CTB (OVA-CT and OVA-CTB). DC pulsed with OVA or with OVA and CTB gave rise to modest antibody and T-cell responses. Conjugation of OVA with CTB enhanced both the subsequent B-cell and T-cell responses to OVA and preferentially induced Th2 responses. CT was shown to be a strong adjuvant when it was coadministered to DC with OVA and was even stronger when it was coadministered with OVA-CTB and primed for a mixed Th1-Th2 response. The antibody and T-cell responses were further enhanced if OVA was coupled to CT, implying that CT can utilize a combined carrier and adjuvant function vis-a-vis linked antigens for DC vaccination. The immunopotentiating capacity of CT- and CTB-linked antigen was associated with both upregulated secretion of interleukin-1beta by the pulsed DC and increased expression of CD80 and CD86 on the DC surface. These results imply that CT and CTB can be used to both markedly increase and partially direct the DC vaccine-induced immune response with respect to Th1 and Th2 responses, which has obvious implications for DC-based vaccine development.