Protection against genital herpes infection in mice immunized under different hormonal conditions correlates with induction of vagina-associated lymphoid tissue
Protection against genital herpes infection in mice immunized under different hormonal conditions correlates with induction of vagina-associated lymphoid tissue
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DOI：
10.1128/jvi.79.5.3117-3126.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Kaushic, C
中科院分区：
文献类型：
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作者：
Gillgrass, AE;Tang, VA;Kaushic, C
本研究旨在研究激素环境对单纯疱疹病毒2型（HSV-2 TK-）减毒株免疫的影响以及随后对攻击的保护作用。切除卵巢的小鼠分别给予生理盐水（S；对照）、雌二醇（E-2）、孕酮（P-4）或雌二醇和孕酮的联合（E+P），并用HSV-2 TK-进行阴道免疫（IVAG）。三周后，免疫小鼠用野生型HSV-2攻击IVAG。在E处理后免疫的小鼠没有受到保护，而S-和p -4处理组的小鼠对攻击有完全的保护。在p -4处理组中，15%的小鼠在TK免疫后出现慢性病理。有趣的是，大约40%接受E+ p治疗的小鼠也受到了保护。在检查阴道分泌物中的病毒脱落后，很明显，对攻击的保护取决于TK-病毒在不同激素条件下引起生殖道感染的能力。在受保护小鼠（S和P组以及部分E+P组）中，刺激后第2天至第5天，阴道固有层短暂形成由CD11c（+）树突状细胞和CD3（+）和CD4(+) T细胞组成的诱导阴道相关淋巴组织。这些聚集物在未受保护的小鼠（E组和部分E+P组）中不存在。在保护小鼠的局部引流淋巴结中观察到明显的hsv -2特异性淋巴细胞活化。在未受保护的组中没有这种反应。在HSV-2攻击后，S-和p4处理的免疫小鼠阴道分泌物中存在高滴度的gb特异性局部免疫球蛋白A （IgA）抗体。s处理组小鼠也具有高的gb特异性IgG滴度。这些研究表明，性激素改变了IVAG免疫后保护性免疫反应的诱导。
The present study was undertaken to examine the effect of the hormonal environment on immunization with an attenuated strain of herpes simplex virus type 2 (HSV-2 TK-) and subsequent protection against challenge. Ovariectomized mice were administered saline (S; control), estradiol (E-2), progesterone (P-4), or a combination of estradiol and progesterone (E+P) and immunized intravaginally (IVAG) with HSV-2 TK-. Three weeks later, the immunized mice were challenged IVAG with wild-type HSV-2. Mice that were immunized following E treatment were not protected, whereas complete protection against the challenge was seen in mice from the S- and P-4-treated groups. In the P-4-treated group, 15% of mice developed chronic pathology following TK- immunization. Interestingly, about 40% of the E+P-treated mice were also protected. Upon examination of viral shedding in the vaginal secretions, it was clear that protection against challenge was dependent on the ability of the TK- virus to cause productive genital infection under different hormonal conditions. In the protected mice (the S and P groups and part of the E+P group), induced vagina-associated lymphoid tissues composed of CD11c(+) dendritic cells and CD3(+) and CD4(+) T cells were formed transiently in the vaginal lamina propria from day 2 to day 5 postchallenge. These aggregates were absent in the unprotected mice (the E group and part of the E+P group). Significant HSV-2-specific activation of lymphocytes was observed in the local draining lymph nodes of protected mice. This response was absent in the unprotected groups. High titers of gB-specific local immunoglobulin A (IgA) antibodies were present in the vaginal secretions of S- and P4-treated immunized mice following HSV-2 challenge. The S-treated group of mice also had high gB-specific IgG titers. These studies show that sex hormones modify the induction of protective immune responses following IVAG immunization.