INFLUENZA VIRUS-INFECTED DENDRITIC CELLS STIMULATE STRONG PROLIFERATIVE AND CYTOLYTIC RESPONSES FROM HUMAN CD8+ T-CELLS
INFLUENZA VIRUS-INFECTED DENDRITIC CELLS STIMULATE STRONG PROLIFERATIVE AND CYTOLYTIC RESPONSES FROM HUMAN CD8+ T-CELLS
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DOI：
10.1172/jci117399
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发表时间：
1994-08-01
影响因子：
15.9
通讯作者：
STEINMAN, RM
中科院分区：
文献类型：
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作者：
BHARDWAJ, N;BENDER, A;STEINMAN, RM
抗原特异性的CD8⁺细胞毒性T淋巴细胞（CTLs）可能对多种感染性疾病和恶性疾病具有抵抗力。然而，在人淋巴细胞培养中产生特异性CTLs的细胞需求尚未明确界定，并且通常需要用抗原进行反复刺激。我们发现，只要树突状细胞用作抗原呈递细胞（APCs），从新鲜分离的血液T细胞就可产生对流感病毒的强烈CD8⁺ CTL反应。少量树突状细胞（APC∶T细胞比例为1∶50 - 1∶100）在7天的培养中可诱导大多数供体产生这些CTL反应，但单核细胞的作用微弱或无活性。虽然树突状细胞和单核细胞都会被流感病毒感染，但前者作为诱导CD8⁺ T细胞的有效APC，而后者则成为所诱导的CTLs的靶细胞。对流感病毒感染的树突状细胞的强烈CD8⁺反应伴随着CD8⁺ T细胞的广泛增殖，但该反应在明显缺乏CD4⁺辅助细胞或外源性淋巴因子的情况下也可产生。树突状细胞也可诱导产生CD4⁺流感病毒特异性CTLs，但培养物最初必须去除CD8⁺细胞。这些发现应该使得利用树突状细胞产生针对其他靶标的人抗原特异性CD8⁺ CTLs成为可能。结果阐明了高效的T细胞介导的反应分两个阶段发展的原理：一个传入支，其中树突状细胞是特化的APC；一个传出支，其中致敏的T细胞对多种类型的呈递细胞执行免疫反应。
Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells.