title: Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.
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.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Penaloza-MacMaster
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Provine
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Teigler
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Parenteau
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Blackmore
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Larocca
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Yates
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: W Nicholas
authors.initials: WN
authors.lastname: Haining
authors.affiliation: Department of Pathology and Immunology, WHO Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Rami
authors.initials: R
authors.lastname: Sommerstein
authors.affiliation: 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.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: 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.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007154:Immune System Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007156:Immunologic Memory; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000209:etiology; D014611:Vaccination; D019562:Viral Load; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D014765:Viral Vaccines