Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells
Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells
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DOI：
10.1084/jem.20021091
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发表时间：
2003-04-07
影响因子：
15.3
通讯作者：
Cella, M
中科院分区：
文献类型：
--
作者：
Krug, A;Veeraswamy, R;Cella, M
干扰素产生细胞（IPC）分泌高水平的I型干扰素以响应某些病毒。由于缺乏谱系标志物、表达主要组织相容性复合物（MHC）II类和刺激同种异体T细胞的能力，这些细胞被归类为树突状细胞（DC）的一个亚群，称为浆细胞样DC（PDCs）。然而，IPC/PDC在启动初次免疫应答中的作用仍然难以捉摸。在这里，我们研究了抗原特异性系统中小鼠IPC的抗原呈递能力。虽然CD8 α（+）和CD11b（+）DC诱导初始CD4和CD8 T细胞的对数扩增，但在第一次接触时不赋予T辅助细胞定型，原代IPC缺乏刺激初始T细胞的能力。然而，当经典DC亚群扩增的抗原经历的非极化T细胞被IPC再刺激时，它们增殖并产生大量IFN-γ。这些数据表明，IPC可以有效地刺激预激活或记忆型T细胞，发挥免疫调节作用。他们还表明，抗原特异性T细胞应答期间幼稚T细胞的扩增和效应子功能的获得可能涉及不同的抗原呈递细胞（APC）类型。T细胞增殖和分化的独立和协调控制将为免疫系统提供更大的调节免疫应答的灵活性。
Interferon-producing cells (IPCs) secrete high levels of type I interferon in response to certain viruses. The lack of lineage markers, the expression of major histocompatibility complex (MHC) class II and the capacity to stimulate allogeneic T cells have led these cells to be classified as a subset of dendritic cells (DCs), called plasmacytoid DCs (PDCs). However, the role of IPCs/PDCs in initiating primary immune responses remains elusive. Here we examined the antigen presenting capacity of murine IPCs in antigen specific systems. While CD8alpha(+) and CD11b(+) DCs induced logarithmic expansion of naive CD4 and CD8 T cells, without conferring T helper commitment at a first encounter, primary IPCs lacked the ability to stimulate naive T cells. However, when antigen-experienced, nonpolarized T cells expanded by classical DC subsets, were restimulated by IPCs, they proliferated and produced high amounts of IFN-gamma. These data indicate that IPCs can effectively stimulate preactivated or memory-type T cells and exert an immune-regulatory role. They also suggest that expansion of naive T cells and acquisition of effector function during antigen-specific T cell responses may involve different antigen-presenting cell (APC) types. Independent and coordinated control of T cell proliferation and differentiation would provide the immune system with greater flexibility in regulating immune responses.