Science. 2015 Jan 16; 347(6219):278-82.

PubMed ID: 25593185

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

Penaloza-MacMaster P, Barber DL, Wherry EJ, Provine NM, Teigler JE, Parenteau L, Blackmore S, Borducchi EN, Larocca RA, Yates KB, Shen H, Haining WN, Sommerstein R, Pinschewer DD, Ahmed R, Barouch DH

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.