Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.

Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.
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DOI:
10.1084/jem.184.5.1879
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发表时间:
1996-11-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Rosenthal KL
Rosenthal KL
中科院分区:
其他
文献类型:
--
作者:
Gallichan WS;Rosenthal KL

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在黏膜表面诱导和维持长期的细胞毒性T淋巴细胞(CTL)记忆可能是抵御黏膜病原体的关键组成部分,也是开发有效黏膜疫苗的目标之一。在这些研究中,我们对通过黏膜或全身免疫途径后,在全身以及呼吸道或生殖相关淋巴组织中的短期和长期CTL记忆进行了功能评估。我们的结果表明,用表达单纯疱疹病毒糖蛋白B(gB)的重组腺病毒载体(AdgB8)对小鼠进行免疫后不久,无论接种途径如何,在全身和黏膜免疫区室都能观察到gB特异性CTL记忆反应。相比之下,免疫几个月后,黏膜免疫后回忆性CTL反应仅局限于黏膜淋巴组织,全身免疫后则仅局限于全身淋巴组织。此外,在鼻内免疫后,在黏膜组织中观察到的局限化CTL记忆反应在功能上可持续超过1.5年,并且免疫1年后的CTL前体细胞频率与免疫后不久观察到的频率相当。因此,据我们所知,这是首次从功能上证明黏膜组织中抗病毒记忆性CTL的维持取决于免疫途径和评估时间。这些结果对我们理解功能性T细胞记忆的产生、维持和区室化,以及对黏膜病原体(如单纯疱疹病毒和人类免疫缺陷病毒)疫苗的开发和评估具有重要意义。
The induction and maintenance of long-term CTL memory at mucosal surfaces may be a critical component of protection against mucosal pathogens and is one goal towards development of effective mucosal vaccines. In these studies we have functionally evaluated short and long-term CTL memory in systemic and respiratory or genital-associated lymphoid tissues following mucosal or systemic routes of immunization. Our results indicate that shortly after immunizing mice with a recombinant adenovirus vector expressing glycoprotein B (gB) of herpes simplex virus (AdgB8), gB-specific CTL memory responses were observed in systemic and mucosal immune compartments regardless of the route of inoculation. In contrast, several months after immunization, anamnestic CTL responses compartmentalized exclusively to mucosal or systemic lymphoid tissues after mucosal or systemic immunization, respectively. Furthermore, the compartmentalized CTL memory responses in mucosal tissues were functionally observed for longer than 1.5 yr after intranasal immunization, and CTL precursor frequencies one year after immunization were comparable to those seen shortly after immunization. Therefore, to our knowledge, this is the first functional demonstration that the maintenance of anti-viral memory CTL in mucosal tissues is dependent on the route of immunization and the time of assessment. These results have important implications for our understanding of the development, maintenance, and compartmentalization of functional T cell memory and the development and evaluation of vaccines for mucosal pathogens, such as HSV and HIV.
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