CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection.
CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection.
复制标题
DOI：
10.4049/jimmunol.1200994
复制
发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Ernst JD
中科院分区：
文献类型：
--
作者：
Bold TD;Ernst JD
CD4+和CD8+ T细胞都有助于结核病的免疫，两者都可以产生必要的效应细胞因子IFN-γ。然而，每种细胞类型对体内IFN-γ产生的确切作用和相对贡献尚不完全清楚。为了鉴定和定量在小鼠结核分枝杆菌感染部位产生IFN-γ的细胞，我们使用体外直接细胞内细胞因子染色而不进行再刺激。我们发现CD4+和CD8+细胞在体内主要负责产生这种细胞因子，我们观察到CD4+细胞的比例和肺中产生IFN-γ的CD8+细胞的比例之间存在显著的线性相关性。在缺乏CD4+细胞的情况下，体内活性产生IFN-γ的CD8+细胞比例降低，这表明CD8+效应细胞持续需要CD4+效应细胞来优化IFN-γ的产生。因此，当感染小鼠静脉注射mhc - ii限制性结核分枝杆菌表位肽来刺激体内CD4+细胞时，我们观察到肺部CD4+和CD8+细胞的快速激活。CD8+细胞的间接激活依赖于CD4+细胞的存在，但不依赖于CD8+细胞对IFN-γ的反应。这些数据提供了证据，证明CD4+细胞缺乏会损害CD8+效应细胞产生IFN-γ，并且肺中不同效应T细胞类型之间的持续串扰可能有助于对结核分枝杆菌的保护性免疫反应。相反，这些相互作用中的缺陷可能导致对结核病和其他感染的易感性。
Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. However, the precise role and relative contribution of each cell type to in vivo IFN-γ production are incompletely understood. To identify and quantitate the cells that produce IFN-γ at the site of M. tuberculosis infection in mice, we used direct intracellular cytokine staining ex vivo without restimulation. We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. In the absence of CD4+ cells, a reduced fraction of CD8+ cells were actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. Accordingly, when infected mice were treated intravenously with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells, but independent of IFN-γ responsiveness of the CD8+ cells. These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing crosstalk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. Conversely, defects in these interactions may contribute to susceptibility to TB and other infections.
登录
查看更多内容
免疫相关的GTPase IRGM1通过防止干扰素γ诱导的细胞死亡促进活化的CD4+ T细胞群体的扩张。
影响因子：
30.5
作者：
Feng, Carl G.;Zheng, Lixin;Jankovic, Dragana;Bafica, Andre;Cannons, Jennifer L.;Watford, Wendy T.;Chaussabel, Damien;Hieny, Sara;Caspar, Patricia;Schwartzberg, Pamela L.;Lenardo, Michael J.;Sher, Alan
通讯作者：
Sher, Alan
影响因子：
32.4
作者：
Egen JG;Rothfuchs AG;Feng CG;Horwitz MA;Sher A;Germain RN
通讯作者：
Germain RN
影响因子：
6.7
作者：
Bold TD;Banaei N;Wolf AJ;Ernst JD
通讯作者：
Ernst JD
影响因子：
4.4
作者：
Liu, F;Whitton, JL
通讯作者：
Whitton, JL
DOI：
10.1073/pnas.1203543109
发表时间：
2012-06-19
影响因子：
11.1
作者：
Freeman, Bailey E.;Hammarlund, Erika;Slifka, Mark K.
通讯作者：
Slifka, Mark K.