Actions of CD4+ T Cells and B Cells During Acute and Persistent Viral Infections Session: Vaccine induced immunopathology mediated by memory CD4 T cells following chronic viral infection (VIR7P.1054)
Pablo Penaloza-MacMaster,
Daniel Barber,
John Wherry,
Nicholas Provine,
Jeffrey Teigler,
Steven Blackmore,
Erica Borducchi,
Roderick Bronson,
and Dan Barouch
J Immunol 2014 192:208.6
Abstract
CD4 T cells are important for promoting functional adaptive immune responses following viral infections, but the specific contribution of vaccine-elicited CD4 T cell responses to immune protection remains unclear. We interrogated whether selective induction of virus-specific CD4 T cell responses by vaccination, in the absence of other adaptive immune responses, would improve immune protection against a chronic lymphocytic choriomeningitis virus (LCMV) challenge in mice. Surprisingly, we observed that immunization of mice with a vaccine that induced predominantly CD4 T cell responses resulted in severe immunopathology and mortality following chronic LCMV clone 13 challenge. Vaccinated mice exhibited impaired adaptive responses, severe inflammation, accelerated destruction of lymphoid tissues, and fulminant mortality as compared with na?ve mice following challenge. This immunopathology was caused by uncontrolled antigen-driven stimulation of memory CD4 T cells that resulted in cytokine storm and widespread inflammation. The adverse effects of vaccination were abrogated by co-immunization with vaccines that generated CD8 T cell responses, adoptive transfer of virus-specific CD8 T cells, or passive immunization with virus-specific immunoglobulins. Altogether, these data raise important concerns for vaccines that predominantly elicit CD4 T cell responses.
