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Science. 2015 Jan 16;347(6219):278-82. doi: 10.1126/science.aaa2148.

Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
2
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
3
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
5
Department of Pathology and Immunology, WHO Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland.
6
Department of Pathology and Immunology, WHO Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland. Department of Biomedicine-Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland.
7
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA. dbarouch@bidmc.harvard.edu.

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.

PMID:
25593185
PMCID:
PMC4382081
DOI:
10.1126/science.aaa2148
[Indexed for MEDLINE]
Free PMC Article

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