Vaccine-elicited CD4 t cells induce immunopathology after chronic lcmv infection

Pablo Penaloza-MacMaster, Daniel L. Barber, E. John Wherry, Nicholas M. Provine, Jeffrey E. Teigler, Lily Parenteau, Stephen Blackmore, Erica N. Borducchi, Rafael A. Larocca, Kathleen B. Yates, Hao Shen, W. Nicholas Haining, Rami Sommerstein, Daniel D. Pinschewer, Rafi Ahmed, Dan H. Barouch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)278-282
Number of pages5
JournalScience
Volume347
Issue number6219
DOIs
StatePublished - Jan 16 2015

ASJC Scopus subject areas

  • General

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