A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell-mediated immunity, priming T cells specific for 2 type III secretion system proteins
A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell-mediated immunity, priming T cells specific for 2 type III secretion system proteins
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DOI：
10.1086/508217
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发表时间：
2006-11-01
影响因子：
6.4
通讯作者：
Bancroft, Gregory J.
中科院分区：
文献类型：
--
作者：
Haque, Ashraful;Chu, Karen;Bancroft, Gregory J.
假鼻疽伯克霍尔德氏菌是类鼻疽病的病原体，类鼻疽病是一种严重的人类疾病，目前还没有疫苗可用。对易感的BALB/c小鼠进行减毒活突变株ilvI(简称“2D2”)免疫，虽然不完全，但产生了显著的免疫力。在免疫的小鼠中检测到的脾假鼻疽特异性T细胞，在体外增殖并产生干扰素-γ，以应对死亡的细菌。对T细胞抗原特异性的评估表明，假鼻疽反应性T细胞亚群对III型分泌系统(TTSS)效应蛋白BOPE有反应，对TTSS转位蛋白BipD的反应程度较小。与单纯T细胞受体相比，过继转移来自免疫小鼠的T细胞可提高严重联合免疫缺陷小鼠的存活率，表明2D2免疫可产生T细胞介导的免疫。体内的CD4(+)和CD8(+)细胞耗竭研究表明，介导这种保护作用的是CD4(+)细胞，而不是CD8(+)细胞。因此，CD4(+)T细胞可以介导疫苗诱导的免疫应答。
Burkholderia pseudomallei is the etiological agent of melioidosis, a serious human disease for which no vaccine is available. Immunization of susceptible BALB/c mice with the live attenuated mutant B. pseudomallei ilvI (referred to as "2D2") generated significant, although incomplete, immunity. Splenic B. pseudomallei-specific T cells, detected in immunized mice, proliferated and produced interferon-gamma in vitro in response to dead bacteria. Assessment of T cell antigen specificity indicated that subpopulations of B. pseudomallei-reactive T cells were responsive to BopE, a type III secretion system (TTSS) effector protein, and to a lesser extent to BipD, a TTSS translocator protein. Increased survival of severe combined immunodeficient mice adoptively transferred with T cells from immunized mice, compared with that of naive T cell recipients, demonstrated that immunization with 2D2 generated T cell-mediated immunity. CD4(+) and CD8(+) cell depletion studies demonstrated that CD4(+) cells, but not CD8(+) cells, mediated this protection in vivo. Thus, CD4(+) T cells can mediate vaccine-induced immunity to experimental melioidosis.