CD8α+ and CD11b+ dendritic cell-restricted MHC class II controls Th1CD4+ T cell immunity
CD8α+ and CD11b+ dendritic cell-restricted MHC class II controls Th1CD4+ T cell immunity
复制标题
DOI：
10.4049/jimmunol.171.10.5077
复制
发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Laufer, TM
中科院分区：
文献类型：
--
作者：
Lemos, MP;Fan, L;Laufer, TM
CD 4 T细胞的活化、增殖、分化和运输对于I型免疫应答的发展至关重要。携带MHC II类（MHCII）的树突状细胞（DCs）启动CD 4（+）T细胞引发，但其他MHCII+ APC对完整的Th 1免疫应答的相对贡献尚不清楚。为了解决这个问题，我们在小鼠模型中检测了Th 1免疫，其中I-A（beta）（B）表达特异性靶向I-A（beta）B-/-小鼠的DC。MHCII表达在CD 11 B（+）和CD 8 α（+）DC中重建，但其它DC亚型、巨噬细胞、B细胞和实质细胞缺乏I-A（β）B链的表达。这些DC亚群对抗原肽和蛋白质的提呈足以使抗原特异性CD 4（+）T细胞在体内分化为Th 1细胞。因此，Ag特异性CD 4（+）T细胞被引发以产生Th 1细胞因子IL-2和IFN-γ。此外，增殖、淋巴器官外的迁移和效应CD 4 + T细胞的数量受到适当调节。然而，II类阴性B细胞不能接受帮助，Ag特异性IgG不产生，证实了在此阶段的关键MHCII需求。这些发现表明，DC不仅是初次免疫应答的关键启动者，而且在初次免疫应答期间提供所有必要的同源相互作用以控制CD 4（+）T细胞的命运。
The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to the development of type I immune responses. MHC class II (MHCII)-bearing dendritic cells (DCs) initiate CD4(+) T cell priming, but the relative contributions of other MHCII+ APCs to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-A(beta)(b) expression was targeted specifically to the DCs of I-A(beta)b-/- mice. MHCII expression is reconstituted in CD11b(+) and CD8alpha(+) DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells lack of expression of the I-A(beta)b chain. Presentation of both peptide and protein Ags by these DC subsets is sufficient for Th1 differentiation of Ag-specific CD4(+) T cells in vivo. Thus, Ag-specific CD4(+) T cells are primed to produce Th1 cytokines IL-2 and IFN-gamma. Additionally, proliferation, migration out of lymphoid organs, and the number of effector CD4+ T cells are appropriately regulated. However, class II-negative B cells cannot receive help and Ag-specific IgG is not produced, confirming the critical MHCII requirement at this stage. These findings indicate that DCs are not only key initiators of the primary response, but provide all of the necessary cognate interactions to control CD4(+) T cell fate during the primary immune response.