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

doi:10.1126/science.aaa2148

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

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

Authors

Pablo Penaloza-MacMaster¹, Daniel L Barber², E John Wherry³, Nicholas M Provine¹, Jeffrey E Teigler¹, Lily Parenteau¹, Stephen Blackmore¹, Erica N Borducchi¹, Rafael A Larocca¹, Kathleen B Yates⁴, Hao Shen³, W Nicholas Haining⁴, Rami Sommerstein⁵, Daniel D Pinschewer⁶, Rafi Ahmed⁷, Dan H Barouch⁸

Affiliations

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. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity
Animals
Antibodies, Viral / immunology
Antigens, Viral / immunology
Arenaviridae Infections / immunology*
Arenaviridae Infections / virology
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology
Cytokines / blood
Epitopes, T-Lymphocyte / immunology
Immune System Diseases / etiology*
Immune System Diseases / immunology
Immune System Diseases / pathology
Immunologic Memory
Inflammation / etiology*
Inflammation / immunology
Inflammation / pathology
Lymphocytic choriomeningitis virus / immunology*
Lymphocytic choriomeningitis virus / physiology
Mice, Inbred C57BL
Multiple Organ Failure / etiology
Vaccination
Viral Load
Viral Vaccines / adverse effects*
Viral Vaccines / immunology*
Virus Replication

Substances

Antibodies, Viral
Antigens, Viral
Cytokines
Epitopes, T-Lymphocyte
Viral Vaccines

Associated data

GEO/GSE63825

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding