Protection of mice and guinea pigs against tuberculosis induced by immunization with a single Mycobacterium tuberculosis recombinant antigen, MTB41
Protection of mice and guinea pigs against tuberculosis induced by immunization with a single Mycobacterium tuberculosis recombinant antigen, MTB41
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DOI：
10.1016/j.vaccine.2005.03.003
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发表时间：
2005-06-10
期刊：
影响因子：
5.5
通讯作者：
Campos-Neto, A
中科院分区：
文献类型：
--
作者：
Skeiky, YAW;Alderson, MR;Campos-Neto, A
MTB41是一种分枝杆菌抗原，在实验感染结核分枝杆菌小鼠后早期被CD4(+) T细胞和来自健康PPD阳性个体的PBMC识别。用编码MTB41基因序列的质粒DNA免疫小鼠可产生抗原特异性CD4（+）和CD8(+) T细胞，并保护小鼠免受致病性结核分枝杆菌的攻击。在目前的研究中，与DNA免疫相比，我们发现在感染小鼠的脾脏细胞中检测到强烈的mtb41特异性CD4(+) T细胞反应，但没有MHC I类限制性细胞毒性T淋巴细胞（CTL）活性。因此，这些数据表明，DNA免疫诱导CD8(+) T细胞对MTB41表位的反应可能与保护无关，因为这些表位在感染过程中不被识别。我们还比较了结核分枝杆菌感染小鼠CD4(+) T细胞对rMTB41表位的识别库与重组rMTB41蛋白免疫小鼠的识别库。两种增敏方案导致识别相同的分子表位。巧合的是，用可溶性重组蛋白加佐剂（一种已知主要产生CD4(+) T细胞的方案）免疫，在两种已建立的结核病动物模型（小鼠和豚鼠）中产生了与卡介苗相当的保护作用。(c) 2005 Elsevier Ltd版权所有。
MTB41 is a mycobacterium antigen that is recognized by CD4(+) T cells early after experimental infection of mice with Mycobacterium tuberculosis and by PBMC from healthy PPD positive individuals. Immunization of mice with plasmid DNA encoding the MTB41 gene sequence results in the development of antigen-specific CD4(+) and CD8(+) T cells, and protection against challenge with virulent M. tuberculosis. In the present studies, in contrast to DNA immunization, we show, that a strong MTB41-specific CD4(+) T cell response, but no MHC class I restricted cytotoxic T lymphocyte (CTL) activity is detected in the spleen cells of infected mice. Therefore, this data suggests that the induction of CD8(+) T cell response to MTB41 epitopes by DNA immunization may not be relevant to protection because these epitopes are not recognized during the infectious process. We also compared the repertoire of rMTB41 epitope recognition by CD4(+) T cells of M. tuberculosis-infected mice with the recognition repertoire of mice immunized with the recombinant rMTB41 protein. Both regimens of sensitization lead to the recognition of the same molecular epitope. Coincidentally, immunization with the soluble recombinant protein plus adjuvant, a regimen known to generate primarily CD4(+) T cells, resulted in induction of protection comparable to BCG in two well-established animal models of tuberculosis (mice and guinea pigs). (c) 2005 Elsevier Ltd. All rights reserved.