Austyn J M
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, United Kingdom.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 2):S146-50. doi: 10.1164/ajrccm.162.supplement_3.15tac1a.
We present a summary of our experimental and clinical studies of dendritic cells (DCs) in five different areas. First, human DCs undergo chemotaxis and transendothelial migration in response to distinct chemokines, depending on their maturation state; inducible chemokines may recruit immature DCs to sites of inflammation and infection, whereas constitutive chemokines may regulate subsequent migration to lymphoid tissues. Second, M-tropic but not T-tropic strains of HIV-1 induce and modulate DC chemotaxis in culture; conceivably this may facilitate viral infection and contribute to pathogenesis in vivo. Third, malaria-infected erythrocytes modulate the maturation and inhibit the function of DCs; adhesion of infected erythrocytes to DCs may impart a selective advantage to the parasite by modulating host immunity. Fourth, a phase I clinical trial of DC-based immunotherapy of cancer has been initiated in which autologous DCs are administered directly into metastatic skin lesions; immune responses to a recall antigen, with which the cells were pulsed, were enhanced in several patients. Finally we describe the growth and characterization of a stably immature, maturation-resistant stage of DCs generated from mouse bone marrow that can induce transplantation tolerance in vivo, and outline studies of their capacity to induce responses of transgenic T cells in vivo.
我们总结了在五个不同领域对树突状细胞（DCs）进行的实验和临床研究。首先，人类DCs根据其成熟状态，对不同的趋化因子产生趋化作用并进行跨内皮迁移；诱导性趋化因子可能将未成熟DCs募集到炎症和感染部位，而组成型趋化因子可能调节随后向淋巴组织的迁移。其次，HIV-1的M嗜性而非T嗜性毒株在培养中诱导并调节DC趋化作用；可以想象，这可能促进病毒感染并在体内导致发病机制。第三，感染疟疾的红细胞调节DCs的成熟并抑制其功能；感染的红细胞与DCs的黏附可能通过调节宿主免疫为寄生虫带来选择性优势。第四，已经启动了一项基于DC的癌症免疫疗法的I期临床试验，其中将自体DCs直接注入转移性皮肤病变；在几名患者中，对细胞脉冲使用的回忆抗原的免疫反应得到增强。最后，我们描述了从小鼠骨髓产生的稳定未成熟、抗成熟阶段的DCs的生长和特性，其可在体内诱导移植耐受，并概述了它们在体内诱导转基因T细胞反应能力的研究。
