Kolumam Ganesh A, Thomas Sunil, Thompson Lucas J, Sprent Jonathan, Murali-Krishna Kaja
Department of Immunology, University of Washington, Seattle, 98195, USA.
J Exp Med. 2005 Sep 5;202(5):637-50. doi: 10.1084/jem.20050821. Epub 2005 Aug 29.
T cell expansion and memory formation are generally more effective when elicited by live organisms than by inactivated vaccines. Elucidation of the underlying mechanisms is important for vaccination and therapeutic strategies. We show that the massive expansion of antigen-specific CD8 T cells that occurs in response to viral infection is critically dependent on the direct action of type I interferons (IFN-Is) on CD8 T cells. By examining the response to infection with lymphocytic choriomeningitis virus using IFN-I receptor-deficient (IFN-IR(0)) and -sufficient CD8 T cells adoptively transferred into normal IFN-IR wild-type hosts, we show that the lack of direct CD8 T cell contact with IFN-I causes >99% reduction in their capacity to expand and generate memory cells. The diminished expansion of IFN-IR(0) CD8 T cells was not caused by a defect in proliferation but by poor survival during the antigen-driven proliferation phase. Thus, IFN-IR signaling in CD8 T cells is critical for the generation of effector and memory cells in response to viral infection.
一般来说，活生物体引发的T细胞扩增和记忆形成比灭活疫苗更有效。阐明其潜在机制对疫苗接种和治疗策略很重要。我们发现，病毒感染后发生的抗原特异性CD8 T细胞的大量扩增严重依赖于I型干扰素（IFN-Is）对CD8 T细胞的直接作用。通过使用IFN-I受体缺陷（IFN-IR(0)）和充足的CD8 T细胞过继转移到正常IFN-IR野生型宿主中，检测对淋巴细胞性脉络丛脑膜炎病毒感染的反应，我们发现CD8 T细胞缺乏与IFN-I的直接接触会导致其扩增和产生记忆细胞的能力降低>99%。IFN-IR(0) CD8 T细胞扩增减少不是由增殖缺陷引起的，而是由抗原驱动增殖阶段的存活率低所致。因此，CD8 T细胞中的IFN-IR信号对于响应病毒感染产生效应细胞和记忆细胞至关重要。
