Milligan G N, Bernstein D I
Division of Clinical Virology, James N. Gamble Institute of Medical Research, Cincinnati, Ohio 45219, USA.
Virology. 1995 Oct 1;212(2):481-9. doi: 10.1006/viro.1995.1506.
A murine model of genital infection with a thymidine kinase-deficient (tk-) strain of herpes simplex virus type 2 (HSV-2) was utilized to examine the development of the local T cell response in the genital mucosa and draining genital lymph nodes (gLN). HSV-specific cytokine-secreting T cells were detected in the gLN 4 days postintravaginal inoculation but not in the urogenital tract or spleen until 5 days postinoculation, suggesting the cellular immune response originates in the gLN. More CD4+ than CD8+ gLN T cells were detected by flow cytometric analysis following primary vaginal inoculation and the majority of HSV-specific gLN T cells detected by ELISPOT were CD4+ and Th1-like based on secretion of IFN gamma and not IL-4 or IL-5. A similar population of HSV-specific memory T cells persisted in the genital tract 2 months following HSV-2 tk- genital inoculation. These data suggest that the urogenital cellular immune response elicited in mice following genital inoculation with HSV-2 tk- is predominantly CD4+ and Th1-like, resembling that observed in humans. The results of this study are important for the rational design of vaccines capable of inducing protective immunity in the genital tract.
利用单纯疱疹病毒2型(HSV - 2)胸苷激酶缺陷(tk -)株建立的小鼠生殖器感染模型,来研究生殖器黏膜和引流生殖器淋巴结(gLN)中局部T细胞反应的发展。阴道内接种后4天在gLN中检测到HSV特异性分泌细胞因子的T细胞,但直到接种后5天在泌尿生殖道或脾脏中才检测到,这表明细胞免疫反应起源于gLN。初次阴道接种后通过流式细胞术分析检测到的gLN T细胞中CD4 +细胞比CD8 +细胞更多,并且基于ELISPOT检测到的大多数HSV特异性gLN T细胞是CD4 +且类似Th1型,因为它们分泌IFNγ而不是IL - 4或IL - 5。HSV - 2 tk -生殖器接种后2个月,类似的HSV特异性记忆T细胞群体持续存在于生殖道中。这些数据表明,小鼠生殖器接种HSV - 2 tk -后引发的泌尿生殖细胞免疫反应主要是CD4 +且类似Th1型,类似于在人类中观察到的情况。本研究结果对于合理设计能够在生殖道中诱导保护性免疫的疫苗具有重要意义。