Immunopathology in RSV Infection Is Mediated by a Discrete Oligoclonal Subset of Antigen-Specific CD4 + T Cells

Abstract

Vaccination with the respiratory syncytial virus (RSV) attachment (G) protein results in immune-mediated lung injury after natural RSV infection with pathogenic features characteristic of an exaggerated Th2 response. Here we demonstrate that approximately half of the CD4 + T cells infiltrating the lungs of G-primed mice utilize a single Vβ gene (Vβ14) with remarkably limited CDR3 diversity. Furthermore, elimination of these Vβ14-bearing CD4 + T cells in vivo abolishes the type 2-like pulmonary injury. These results suggest that a novel subset of CD4 + T cells may be crucial in the development of pathology during human RSV infection and that genetic or environmental factors prior to or at the time of G antigen exposure may affect the commitment of this discrete antigen-specific T cell subset to Th2 differentiation.