Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract
Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a functional effector memory T cell population that persists in the murine genital tract
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DOI：
10.1016/j.jri.2010.06.155
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发表时间：
2010-12-01
影响因子：
3.4
通讯作者：
Rosenthal, Kenneth L.
中科院分区：
文献类型：
--
作者：
Tang, Vera A.;Rosenthal, Kenneth L.
尽管女性生殖道是女性性传播感染的主要入口，但我们对局部组织中记忆T细胞的生成、维持和特征的了解仍然有限。在这里，我们利用阴道内 HSV-2 感染和针对 CD8+ T 细胞识别的免疫显性 HSV 糖蛋白 B 表位的四聚体的小鼠模型来检查急性感染后生殖道中抗 HSV 记忆 T 细胞的生成、维持和特征。我们的结果表明，与脾脏或髂淋巴结相比，在生殖道中发现了最高百分比的 HSVgB 特异性 CD8+ T 细胞。事实上，尽管病毒清除后 CD8+ T 细胞的实际数量有所收缩，但生殖器组织中保留的 CD8+ 细胞群中大约四分之一是 HSVgB 特异性的。生殖道中的记忆gB-四聚体+CD8 T细胞CD127和KLRG1呈阳性，CD62L和CCR7呈阴性，从而证实HSV特异性CD8细胞是缺乏归巢至淋巴组织的能力的效应记忆T细胞。从功能上讲，生殖道中的记忆性 CD8+ 和 CD4+ HSV 特异性群体在体外受到刺激时都会产生 IFN γ，而 CD4+ 细胞也会产生 TNF α。生殖器 HSVgB 特异性记忆 T 细胞表达组织归巢整合素 CD103（α E 整合素）和 CD49a（VLA-1 或 α 1 整合素）。我们的研究结果表明，HSV 特异性记忆 T 细胞保留在生殖道中，准备作为未来病毒遭遇的早期防线。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Although the female genital tract is the main portal of entry for sexually transmitted infections in women, we still have limited understanding of the generation, maintenance and characteristics of memory T cells in the local tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and tetramers against the immunodominant HSV glycoprotein B epitope recognized by CD8+ T cells to examine the generation, maintenance and characteristics of anti-HSV memory T cells in the genital tract following acute infection. Our results show that the highest percentage of HSVgB-specific CD8+ T cells was found in the genital tract compared to the spleen or iliac lymphnode. Indeed, although the actual number of CD8+ T cells contracted following viral clearance, approximately one quarter of the CD8+ population that remained in the genital tissue was HSVgB-specific. Memory gB-tetramer +CD8 T cells in the genital tract were positive for CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV-specific CD8 cells were effector memory T cells that lack the capacity for homing to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific populations in the genital tract produced IFN gamma when stimulated in vitro and CD4+ cells also produced TNF alpha. Genital HSVgB-specific memory T cells expressed tissue-homing integrins CD103 (alpha E integrin) and CD49a (VLA-1 or alpha 1 integrin). Our findings suggest that HSV-specific memory T cells are retained in the genital tract, poised to act as an early line of defense against future virus encounter. (C) 2010 Elsevier Ireland Ltd. All rights reserved.