Immunopathology in RSV infection is mediated by a discrete oligoclonal subset of antigen-specific CD4(+) T cells.
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 V beta gene (V beta 14) with remarkably limited CDR3 diversity. Furthermore, elimination of these V beta 14-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.
Varga
S M
SM
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Wang
X
X
Welsh
R M
RM
Braciale
T J
TJ
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification; D018418:Th2 Cells / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014764:Viral Proteins