A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection
A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection
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DOI：
10.4049/jimmunol.175.11.7536
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Morrison, RP
中科院分区：
文献类型：
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作者：
Morrison, SG;Morrison, RP
长期以来，人们一直认为对生殖道沙眼衣原体再感染的获得性免疫仅依赖于细胞免疫。然而，在这项研究中，我们确定了一个以前未被认识到的保护作用抗体。免疫力的发展，在抗体缺陷小鼠的决议后，原发性衣原体生殖器感染。在二次感染攻击前，这些免疫Ab缺陷小鼠中的CD4（+）T细胞随后耗竭，但CD8（+）T细胞未耗竭，导致感染未消退。用免疫（恢复期）血清进行被动免疫可产生显著水平的保护性免疫力，防止再感染，其特征是细菌脱落显著减少，从> 100，000个包涵体形成单位减少到小于10个包涵体形成单位，并缩短感染持续时间。此外，针对衣原体主要外膜蛋白和LPS的mAb赋予了对再感染的显著水平的免疫力，并使衣原体脱落减少> 100倍。抗热休克蛋白60单克隆抗体无保护作用。与免疫血清对再感染的显著保护作用相反，免疫血清的被动转移基本上不改变原发感染的过程。我们的研究结果令人信服地表明，抗体有助于重要的免疫衣原体生殖道再感染，抗体介导的保护是高度依赖于CD4（+）T细胞介导的适应性变化，发生在局部生殖道组织在原发感染。这些结果影响了我们对衣原体生殖器感染免疫的理解，并可能为疫苗开发提供重要的见解。
Acquired immunity to murine Chlamydia trachomatis genital tract reinfection has long been assumed to be solely dependent on cell-mediated immunity. However, in this study, we identify a previously unrecognized protective role for Ab. Immunity develops in Ab-deficient mice following the resolution of primary chlamydial genital infection. Subsequent depletion of CD4(+) T cells, but not CD8(+) T cells, in those immune Ab-deficient mice before secondary infectious challenge, resulted in an infection that did not resolve. Passive immunization with immune (convalescent) serum conferred a marked level of protective immunity to reinfection, which was characterized by a striking decrease in bacterial shedding, from > 100,000 inclusion forming units to fewer than 10 inclusion forming units, and a shortened duration of infection. Furthermore, mAbs to the chlamydial major outer membrane protein and LPS conferred significant levels of immunity to reinfection and reduced chlamydial shedding by > 100-fold. Anti-heat shock protein 60 mAb had no protective effect. In contrast to the marked protective efficacy of immune serum on reinfection, the course of primary infection was essentially unaltered by the passive transfer of immune serum. Our results convincingly demonstrate that Abs contribute importantly to immunity to chlamydial genital tract reinfection, and that Ab-mediated protection is highly dependent on CD4(+) T cell-mediated adaptive changes that occur in the local genital tract tissues during primary infection. These results impact our understanding of immunity to chlamydial genital infection and may provide important insight into vaccine development.