Posavad Christine M, Wald Anna, Hosken Nancy, Huang Meei Li, Koelle David M, Ashley Rhoda L, Corey Lawrence
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98104, USA.
J Immunol. 2003 Apr 15;170(8):4380-8. doi: 10.4049/jimmunol.170.8.4380.
During the course of investigating T cell responses to HSV among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed HSV-specific T cell immunity but, by multiple determinants of even the most sensitive serological assays, remained seronegative to HSV-1 and -2. Of these six immune seronegative (IS; HSV-seronegative with HSV-specific T cell responses) subjects, two had transient HSV-specific T cell responses, while four had CD4(+) and CD8(+) T cell responses directed at HSV that persisted for up to 4 years. CD4(+) T cell clones were isolated that recognized and had high binding affinities to epitopes in HSV-2 tegument proteins. All six IS subjects had potential sexual exposure to an HSV-2-infected sexual partner. Oral and genital mucosal secretions were sampled and tested for the presence of infectious HSV and HSV DNA. No evidence of HSV was detected in >1500 samples obtained from these IS subjects. The identification of persistent T cell responses to HSV in seronegative subjects is a novel finding in the herpesvirus field and suggests either undetected infection or acquired immunity in the absence of infection. Understanding the basis of these acquired immune responses may be critical in developing effective vaccines for genital herpes.
在对参与研究性生殖器疱疹疫苗试验的志愿者进行T细胞对单纯疱疹病毒(HSV)反应的调查过程中,24名既往无口腔/唇或生殖器疱疹病史的免疫功能正常受试者中,有6人具备HSV特异性T细胞免疫,但即便采用最敏感血清学检测的多项指标,他们对HSV-1和HSV-2仍呈血清学阴性。在这6名免疫血清学阴性(IS;HSV血清学阴性但有HSV特异性T细胞反应)的受试者中,2人有短暂的HSV特异性T细胞反应,而另外4人的针对HSV的CD4(+)和CD8(+) T细胞反应持续了长达4年。分离出了对HSV-2被膜蛋白表位具有识别能力且结合亲和力高的CD4(+) T细胞克隆。所有6名IS受试者都有可能与感染HSV-2的性伴侣有过性接触。采集了口腔和生殖器黏膜分泌物样本并检测其中是否存在感染性HSV和HSV DNA。在从这些IS受试者获取的1500多个样本中未检测到HSV的迹象。血清学阴性受试者中存在对HSV的持续性T细胞反应这一发现,在疱疹病毒领域是一项新发现,提示存在未被检测到的感染或在无感染情况下获得的免疫力。了解这些获得性免疫反应的基础,对于开发有效的生殖器疱疹疫苗可能至关重要。