Serbina N V, Flynn J L
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Infect Immun. 2001 Jul;69(7):4320-8. doi: 10.1128/IAI.69.7.4320-4328.2001.
The contribution of CD8(+) T cells to the control of tuberculosis has been studied primarily during acute infection in mouse models. Memory or recall responses in tuberculosis are less well characterized, particularly with respect to the CD8 T-cell subset. In fact, there are published reports that CD8(+) T cells do not participate in the memory immune response to Mycobacterium tuberculosis. We examined the CD8(+) T-cell memory and local recall response to M. tuberculosis. To establish a memory immunity model, C57BL/6 mice were infected with M. tuberculosis, followed by treatment with anti-mycobacterial drugs and prolonged rest. The lungs of memory immune mice contained CD4(+) and CD8(+) T cells with the cell surface phenotype characteristic of memory cells (CD69(low) CD25(low) CD44(high)). At 1 week postchallenge with M. tuberculosis via aerosol, > or =30% of both CD4(+) and CD8(+) T cells in the lungs of immune mice expressed the activation marker CD69 and could be restimulated to produce gamma interferon (IFN-gamma). In contrast, <6% of T cells in the lungs of naive challenged mice were CD69(+) at 1 week postchallenge, and IFN-gamma production was not observed at this time point. CD8(+) T cells from the lungs of both naive and memory mice after challenge were cytotoxic toward M. tuberculosis-infected macrophages. Our data indicate that memory and recall immunity to M. tuberculosis is comprised of both CD4(+) and CD8(+) T lymphocytes and that there is a rapid response of both subsets in the lungs following challenge.
CD8(+) T细胞在结核病控制中的作用主要是在小鼠模型的急性感染期间进行研究的。结核病中的记忆或回忆反应的特征尚不明确,尤其是关于CD8 T细胞亚群。事实上,有已发表的报告称CD8(+) T细胞不参与对结核分枝杆菌的记忆免疫反应。我们研究了CD8(+) T细胞对结核分枝杆菌的记忆和局部回忆反应。为建立记忆免疫模型,用结核分枝杆菌感染C57BL/6小鼠,随后用抗分枝杆菌药物治疗并延长休息时间。记忆免疫小鼠的肺中含有具有记忆细胞特征性细胞表面表型(CD69(low) CD25(low) CD44(high))的CD4(+)和CD8(+) T细胞。在通过气溶胶用结核分枝杆菌攻击后1周,免疫小鼠肺中>或 =30%的CD4(+)和CD8(+) T细胞表达激活标志物CD69,并且可以被再次刺激产生γ干扰素(IFN-γ)。相比之下,未感染对照小鼠肺中的T细胞在攻击后1周<6%为CD69(+),且此时未观察到IFN-γ产生。攻击后来自未感染和记忆小鼠肺中的CD8(+) T细胞对结核分枝杆菌感染的巨噬细胞具有细胞毒性。我们的数据表明,对结核分枝杆菌的记忆和回忆免疫由CD4(+)和CD8(+) T淋巴细胞组成,并且攻击后肺中这两个亚群都会迅速反应。