Division of Immunology, New England Primate Research Center, Harvard Medical School, Pine Hill Drive, Southborough, MA 01772, USA.
Am J Reprod Immunol. 2011 Mar;65(3):242-7. doi: 10.1111/j.1600-0897.2010.00966.x. Epub 2011 Jan 12.
Mucosal T lymphocyte responses in the female reproductive tract, the primary site of HIV transmission in women, may be critical for initial control of virus infection. In addition, characterization of genital immune responses to HIV will be important for the development of a vaccine capable of preventing infection by this route.
We analyzed lymphocytes isolated from vagina and cervix of chronically SIV-infected macaques for the frequency of SIV Gag tetramer-binding cells and expression of chemokine receptors.
We found that the frequency of SIV-specific CD8+ T cell responses was 3- to 30-fold higher in genital tissues than in peripheral blood. SIV-specific CD8+ T cells in genital tissues expressed high levels of CXCR3 and CCR5, chemokine receptors normally expressed on memory T cells that home to inflamed tissues. Cells expressing CXCR3 colocalized with its chemokine ligand CXCL9 [monokine induced by interferon gamma, MIG] in the vaginal lamina propria.
These results indicate that the frequency of SIV-specific CD8+ T cells in the female genital mucosa is enriched compared with peripheral blood and provide initial information regarding the signals that direct recruitment of T cells to the female reproductive tract.
在女性生殖道中,黏膜 T 淋巴细胞的反应可能是控制病毒感染的初始关键,女性生殖道是 HIV 传播的主要部位。此外,对 HIV 引起的生殖器免疫反应进行特征描述,对于开发一种能够预防该途径感染的疫苗非常重要。
我们分析了慢性 SIV 感染猕猴阴道和宫颈分离的淋巴细胞,以研究 SIV Gag 四聚体结合细胞的频率和趋化因子受体的表达。
我们发现,生殖道组织中 SIV 特异性 CD8+T 细胞反应的频率比外周血高 3-30 倍。生殖道组织中的 SIV 特异性 CD8+T 细胞表达高水平的 CXCR3 和 CCR5,这是通常表达在记忆 T 细胞上的趋化因子受体,这些细胞归巢到炎症组织。表达 CXCR3 的细胞与阴道固有层中的趋化因子配体 CXCL9(干扰素 γ诱导的单核细胞趋化蛋白 1,MIG)共定位。
这些结果表明,与外周血相比,女性生殖道黏膜中 SIV 特异性 CD8+T 细胞的频率更为丰富,并提供了有关引导 T 细胞向女性生殖道募集的信号的初步信息。