Irwin Scott M, Izzo Angelo A, Dow Steven W, Skeiky Y A W, Reed Steven G, Alderson Mark R, Orme Ian M
Mycobacterial Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523-1682, USA.
Infect Immun. 2005 Sep;73(9):5809-16. doi: 10.1128/IAI.73.9.5809-5816.2005.
This study used a major histocompatibility complex class I tetramer reagent to track antigen-specific CD8 T cells in the lungs of mice immunized with the tuberculosis vaccine candidate Mtb72F. The results show that CD8 T cells recognizing an immunodominant Mtb32-specific epitope could be detected in significant numbers over the course of infection in mice exposed to low-dose aerosol challenge with Mycobacterium tuberculosis and that prior vaccination substantially increased the numbers of these cells early in the lungs. The effector phenotype of the cells was shown by the demonstration that many secreted gamma interferon, but very few contained granzyme B. As the course of the infection progressed, many activated CD8 T cells down-regulated expression of CD45RB and upregulated expression of the interleukin-7 receptor alpha chain, indicating a transition of these cells to a state of memory. These data support the hypothesis that M. tuberculosis-specific CD8 T cells can be targeted by vaccination with the Mtb72F polyprotein.
本研究使用主要组织相容性复合体I类四聚体试剂来追踪用结核疫苗候选物Mtb72F免疫的小鼠肺内的抗原特异性CD8 T细胞。结果显示,在用结核分枝杆菌低剂量气溶胶攻击的小鼠感染过程中,可大量检测到识别免疫显性Mtb32特异性表位的CD8 T细胞,并且预先接种疫苗可在肺部早期显著增加这些细胞的数量。通过证明许多细胞分泌γ干扰素,但很少细胞含有颗粒酶B,显示了这些细胞的效应表型。随着感染过程的进展,许多活化的CD8 T细胞下调CD45RB的表达并上调白细胞介素-7受体α链的表达,表明这些细胞向记忆状态转变。这些数据支持这样的假设,即结核分枝杆菌特异性CD8 T细胞可以通过接种Mtb72F多蛋白来靶向。