期刊
JOURNAL OF VIROLOGY
卷 76, 期 7, 页码 3329-3337出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.76.7.3329-3337.2002
关键词
-
类别
资金
- NIAID NIH HHS [N01AI30048, AI30048] Funding Source: Medline
Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the W-specific T-cell response and how this compares to the immune response to the foreign gene(s) expressed by the rVV. To address this issue, we quantitated the T-cell responses to both the viral vector and the insert following the infection of mice with W expressing a cytotoxic T lymphocyte (CTL) epitope (NP118-126) from lymphocytic choriomeningitis virus (LCMV). The LCMV epitope-specific response was quantitated by intracellular cytokine staining after stimulation with the specific peptide. To analyze the total VV-specific response, we developed a simple intracellular cytokine staining assay using VV-infected major histocompatibility complex class I and II matched cells as stimulators. Using this approach, we made the following determinations. (i) VV-NP118 induced potent and long-lasting CD8 and CD4 T-cell responses to the vector; at the peak of the response (similar to1 week), there were similar to10(7) VV-specific CD8 T cells (25% of the CD8 T cells) and similar to10(6) VV-specific CD4 T cells (similar to5% of the CD4 T cells) in the spleen. These numbers decreased to similar to5 x 10(5) CD8 T cells (similar to5% frequency) and similar to10(5) CD4 T cells (similar to0.5% frequency), respectively, by day 30 and were then stably maintained at these levels for >300 days. The size of this W-specific T-cell response was comparable to that of the T-cell response induced following an acute LCMV infection. (ii) W-specific CD8 and CD4 T cells were capable of producing gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-2; all cells were able to make IFN-gamma, a subset produced both IFN-gamma and TNF-alpha, and another subset produced all three cytokines. (iii) The CD8 T-cell response to the foreign gene (LCMV NP118-126 epitope) was coordinately regulated with the response to the vector during all three phases (expansion, contraction, and memory) of the T-cell response. The total number of CD8 T cells responding to NP118-126 were similar to20- to 30-fold lower than the number responding to the W vector (similar to1% at the peak and 0.2% in memory). This study provides a better understanding of T-cell immunity induced by W-based vaccines, and in addition, the technique described in the study can be readily extended to other viral vectors to determine the ratio of the T-cell response to the insert versus the vector. This information will be useful in optimizing prime-boost regimens for vaccination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据