CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization
CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization
复制标题
DOI：
10.1073/pnas.0501254102
复制
发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Lipsitch, M
中科院分区：
文献类型：
--
作者：
Malley, R;Trzcinski, K;Lipsitch, M
长期以来，对肺炎链球菌(肺炎球菌)的获得性免疫一直被认为依赖于抗囊抗体的存在。然而，我们发现，用6B、7F或14型活肺炎球菌定植可以保护小鼠免受任何血清型的再繁殖，并且防止获得异源或同源菌株的保护不依赖于抗囊抗体。此外，活体肺炎球菌定植或灭活的无囊膜全细胞疫苗鼻腔免疫可保护抗体缺陷小鼠免受定植，这表明对任何肺炎球菌抗原的抗体都是独立的。全细胞疫苗鼻腔免疫的保护作用在T细胞缺陷的小鼠和在攻击时先天缺乏CD4(+)T细胞或这些细胞耗尽的小鼠中完全取消。相比之下，先天性CD8(+)T细胞缺陷或耗尽的小鼠则完全受到保护。该模型中的保护作用在免疫后2个月以上观察到，反对先天或非特异性免疫机制。因此，我们发现在没有抗体的情况下可以诱导对肺炎球菌定植的免疫，而这种免疫独立于被膜类型，并且这种保护需要在攻击时存在CD4(+)T细胞。
Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend an the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4(+) T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8(+) T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4(+) T cells at the time of challenge.