Dillon S M, Griffin J F, Hart D N, Watson J D, Baird M A
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Immunology. 1998 Sep;95(1):132-40. doi: 10.1046/j.1365-2567.1998.00546.x.
Vaccines against infectious organisms must produce not only long-lasting immunity but also the appropriate immune response to clear the infection. Obligate intracellular parasites, such as mycobacteria, require a predominantly cell-mediated immune response rather than antibody. Presentation of antigen by dendritic cells (DC) has been associated with the development of strong cell-mediated responses generating the production of interferon-gamma (IFN-gamma). This cytokine has an essential role in the elimination of mycobacteria. Therefore, we investigated both the duration and the nature of the immune response after priming with DC pulsed with mycobacterial antigen and compared this with priming using a conventional adjuvant. We used two strains of mice: C57BL/6, which inherently produces a T-helper 1 (Th1)-type response to mycobacterial antigen, and BALB/c, which does not. DC-enriched cell suspensions, purified DC or cultured bone marrow cells resembling DC (BMAPC) were prepared, pulsed overnight with PPD and injected intravenously (i.v.) into naive mice. Six and 12 weeks later, splenic T lymphocytes from these mice were challenged in vitro with antigen and their proliferative response and cytokine production was determined. Significant antigen-specific proliferation was observed in all assays on rechallenge with antigen in vitro 6 and 12 weeks after the initial priming with DC. IFN-gamma was detected in both strains but was only antigen specific in the C57BL/6 strain. Purified protein derivative (PPD)-pulsed BMAPC generated similar responses 6 weeks after priming. Thus, long-term T-lymphocyte responses and the production of IFN-gamma can be generated using a single inoculation of PPD-pulsed DC.
针对传染性生物体的疫苗不仅必须产生持久的免疫力，还必须产生清除感染的适当免疫反应。专性细胞内寄生虫，如分枝杆菌，需要主要由细胞介导的免疫反应而非抗体。树突状细胞（DC）呈递抗原与产生干扰素-γ（IFN-γ）的强烈细胞介导反应的发展有关。这种细胞因子在消除分枝杆菌中起重要作用。因此，我们研究了用分枝杆菌抗原脉冲处理的DC进行初次免疫后免疫反应的持续时间和性质，并将其与使用传统佐剂进行初次免疫的情况进行了比较。我们使用了两种品系的小鼠：C57BL/6，其对分枝杆菌抗原固有地产生辅助性T细胞1（Th1）型反应；以及BALB/c，其不产生这种反应。制备了富含DC的细胞悬液、纯化的DC或类似DC的培养骨髓细胞（BMAPC），用纯化蛋白衍生物（PPD）脉冲处理过夜，然后静脉内（i.v.）注射到未接触过抗原的小鼠体内。6周和12周后，用抗原在体外刺激这些小鼠的脾T淋巴细胞，并测定它们的增殖反应和细胞因子产生情况。在用DC进行初次免疫后6周和12周，在所有体外再次用抗原刺激的试验中均观察到显著的抗原特异性增殖。在两个品系中均检测到IFN-γ，但仅在C57BL/6品系中是抗原特异性的。用PPD脉冲处理的BMAPC在初次免疫6周后产生了类似的反应。因此，使用单次接种PPD脉冲处理的DC可以产生长期的T淋巴细胞反应和IFN-γ的产生。
