Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.
Virus-specific immune memory at peripheral sites of herpes simplex virus type 2 (HSV-2) infection in guinea pigs.
复制标题
DOI：
10.1371/journal.pone.0114652
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Milligan GN
中科院分区：
文献类型：
--
作者：
Xia J;Veselenak RL;Gorder SR;Bourne N;Milligan GN
尽管其在调节HSV-2发病机制中的重要性，但对HSV-2的组织驻留免疫记忆的性质尚未完全了解。我们使用生殖器HSV-2感染的豚鼠，以评估HSV-2感染的外周部位的HSV特异性记忆细胞的类型和位置。HSV-特异性抗体分泌细胞很容易检测到脾脏，骨髓，阴道/宫颈，腰骶感觉神经节，和脊髓的先前感染的动物。记忆B细胞主要在脾脏中检测到，在骨髓中检测到的程度较低，但在生殖道或神经组织中未检测到，这表明HSV-2感染外周部位存在的HSV特异性抗体分泌细胞代表持续存在的浆细胞群体。从感染动物的神经组织分离的这些细胞产生的抗体是功能相关的，包括HSV-2糖蛋白特异性抗体和HSV-2中和抗体。在急性HSV-2感染后，在脾脏以及生殖道、腰骶神经节和脊髓中的HSV-2感染部位产生强烈的IFN-γ分泌性T细胞应答。此外，HSV特异性组织驻留记忆T细胞的群体维持在这些位点，并且在HSV-2感染后长达150天容易检测到。与持续存在的浆细胞不同，HSV特异性记忆T细胞也在子宫组织和脊髓的颈胸区中检测到，并且在颈胸神经节中检测到低水平。HSV-2感染后，生殖道和感觉神经节/脊髓中HSV特异性CD 4+和CD 8+驻留记忆细胞亚群均长期维持。总之，这些数据证明了在HSV-2潜伏期和病毒脱落部位的适应性免疫应答的体液和细胞臂的长期维持，并突出了豚鼠感染模型在HSV-2潜伏期和自发再激活的背景下研究组织驻留记忆的实用性。
Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.
登录
查看更多内容
影响因子：
6.4
作者：
Mark, Karen E.;Wald, Anna;Corey, Lawrence
通讯作者：
Corey, Lawrence
DOI：
10.1084/jem.20082039
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iijima N;Linehan MM;Zamora M;Butkus D;Dunn R;Kehry MR;Laufer TM;Iwasaki A
通讯作者：
Iwasaki A
DOI：
10.1126/science.1164164
发表时间：
2008-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Knickelbein JE;Khanna KM;Yee MB;Baty CJ;Kinchington PR;Hendricks RL
通讯作者：
Hendricks RL
影响因子：
7.6
作者：
Bourne, N;Ireland, J;Bernstein, DI
通讯作者：
Bernstein, DI
影响因子：
5.4
作者：
Da Costa, X;Kramer, MF;Knipe, DM
通讯作者：
Knipe, DM