Freigang Stefan, Egger Denise, Bienz Kurt, Hengartner Hans, Zinkernagel Rolf M
Institute of Experimental Immunology, University Hospital, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13477-82. doi: 10.1073/pnas.1835685100. Epub 2003 Oct 31.
Induction of antiviral cytotoxic T lymphocytes (CTLs) has been proposed to require cross-presentation of viral antigens derived from infected extralymphatic host cells by antigen-presenting cells (APC). This postulated mechanism of cross-priming is thought to be essential for CTL responses against viruses that do not infect professional APC, e.g., because of absence of the specific virus receptor. Here, we show for the human pathogen poliovirus that naturally nonpermissive murine APC acquire viral RNA in vivo independently of the cellular virus receptor. Uptake of poliovirus or polioviral RNA initiated neosynthesis of viral antigen to an extent sufficient to prime CTLs in vivo, which were detectable 2-3 wk after infection. Our results do not only indicate that experiments studying cross-presentation and cross-priming by using potentially amplifiable or translatable materials need careful examination, but they also question the general biological importance of cross-presentation and cross-priming in antiviral CTL responses.
抗病毒细胞毒性T淋巴细胞（CTL）的诱导被认为需要抗原呈递细胞（APC）对源自受感染的淋巴外宿主细胞的病毒抗原进行交叉呈递。这种假定的交叉启动机制被认为对于针对不感染专职APC的病毒的CTL反应至关重要，例如，由于缺乏特定的病毒受体。在这里，我们针对人类病原体脊髓灰质炎病毒表明，天然不允许感染的小鼠APC在体内独立于细胞病毒受体获取病毒RNA。脊髓灰质炎病毒或脊髓灰质炎病毒RNA的摄取引发了病毒抗原的新合成，其程度足以在体内启动CTL，感染后2-3周可检测到。我们的结果不仅表明，使用潜在可扩增或可翻译材料研究交叉呈递和交叉启动的实验需要仔细检查，而且还质疑交叉呈递和交叉启动在抗病毒CTL反应中的一般生物学重要性。
