Penaloza-MacMaster Pablo, Barber Daniel L, Wherry E John, Provine Nicholas M, Teigler Jeffrey E, Parenteau Lily, Blackmore Stephen, Borducchi Erica N, Larocca Rafael A, Yates Kathleen B, Shen Hao, Haining W Nicholas, Sommerstein Rami, Pinschewer Daniel D, Ahmed Rafi, Barouch Dan H
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Science. 2015 Jan 16;347(6219):278-82. doi: 10.1126/science.aaa2148.
CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.
CD4 T细胞可促进先天性和适应性免疫反应，但疫苗诱导产生的CD4 T细胞如何促成免疫保护仍不清楚。我们评估了通过疫苗接种诱导病毒特异性CD4 T细胞是否能保护小鼠免受慢性淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染。用选择性诱导CD4 T细胞反应的疫苗进行免疫接种后，在用持续性LCMV毒株攻击后，导致了灾难性的炎症和死亡。免疫病理学需要抗原特异性CD4 T细胞，并与细胞因子风暴、全身性炎症和多器官系统衰竭有关。病毒特异性CD8 T细胞或抗体可消除这种病理状况。这些数据表明，在缺乏有效的抗病毒免疫反应的情况下，疫苗诱导产生的CD4 T细胞可引发致命的免疫病理学变化。
