Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo.
Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo.
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DOI：
10.1084/jem.177.5.1299
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发表时间：
1993-05-01
期刊：
影响因子：
--
通讯作者：
MacPherson GG
中科院分区：
文献类型：
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作者：
Liu LM;MacPherson GG
在大鼠中，肠系膜淋巴结切除术允许收集来自胸导管插管后小肠的树突状细胞（DC）。我们以这种方式制备大鼠，并通过口服喂养或肠内注射给予抗原。从这些动物的前24小时内收集的胸导管淋巴中富集的DC能够在体外刺激致敏的T细胞，并在足垫注射后引发腘淋巴结CD4+ T细胞，而来自相同胸导管淋巴的B和T细胞在引发中是惰性的。在体外用抗原脉冲的500个或更少的DC可以在体内引发T细胞，而在体外脉冲的100倍以上的B细胞或巨噬细胞是相当惰性的。口服给予Img卵清蛋白足以负载DC用于体内引发T细胞。抗原不能直接在DC中检测到，但存在于固有层中的巨噬细胞中。直接呈递抗原的DC到T细胞被证明通过注射F1受体与亲本DC和显示限制T细胞致敏的主要组织相容性复合物的注射DC。携带抗原的DC不诱导可检测的第一抗体应答，但在加强注射后可以检测到小的第二抗体应答。这些结果表明，DC在肠道中获得抗原与体外或其他组织中发生的情况非常相似，表明粘膜表面的抗原处理可能没有特殊差异。这些结果的一个含义是，设计来解释口服耐受性的假设必须考虑到在接受口服抗原的动物中存在免疫刺激性的、携带抗原的DC。
In the rat, mesenteric lymphadenectomy allows collection of dendritic cells (DC) derived from the small intestine after cannulation of the thoracic duct. We prepared rats this way and administered antigens by oral feeding or intraintestinal injection. DC enriched from the thoracic duct lymph collected over the first 24 h from these animals are able to stimulate sensitized T cells in vitro and to prime popliteal lymph node CD4+ T cells after footpad injection, while B and T cells from the same thoracic duct lymph are inert in priming. 500 or less DC pulsed in vitro with antigen can prime T cells in vivo, whereas 100 times more B cells or macrophages pulsed in vitro are quite inert. 1 mg of ovalbumin administered orally is sufficient to load DC for in vivo priming of T cells. Antigen could not be detected directly in DC but was present in macrophages in the lamina propria. Direct presentation of antigen by DC to T cells was demonstrated by injecting F1 recipients with parental DC and showing restriction of T cell sensitization to the major histocompatibility complex of the injected DC. Antigen-bearing DC do not induce a detectable primary antibody response but a small secondary antibody response can be detected after a boosting injection. These results show that acquisition of antigens by DC in the intestine is very similar to what occurs in vitro or in other tissues, suggesting that there may be no special difference in antigen handling at mucosal surfaces. One implication of these results is that hypotheses designed to explain oral tolerance must take into account the presence of immunostimulatory, antigen-bearing DC in animals that have received oral antigens.