Vbeta14(+) T cells mediate the vaccine-enhanced disease induced by immunization with respiratory syncytial virus (RSV) G glycoprotein but not with formalin-inactivated RSV.
Mice immunized with respiratory syncytial virus (RSV) G glycoprotein or with formalin-inactivated RSV (FI-RSV) exhibit severe disease following RSV challenge. This results in type 2 cytokine production and pulmonary eosinophilia, both hallmarks of vaccine-enhanced disease. RSV G-induced T-cell responses were shown to be restricted to CD4(+) T cells expressing Vbeta14 in the T-cell receptor (TCR), and the deletion of these T cells resulted in less severe disease. We therefore examined the role of Vbeta14(+) T cells in FI-RSV-induced disease. BALB/c mice were immunized with vaccinia virus expressing secreted RSV G (vvGs) or with FI-RSV. At the time of challenge with live RSV, mice were injected with antibody to the Vbeta14 component of the TCR. vvGs-immunized mice treated with anti-Vbeta14 had reduced cytokine levels in the lung. Eosinophil recruitment to the lung was also significantly reduced. In contrast, depletion of Vbeta14(+) T cells in FI-RSV-immunized mice had little impact on cytokine production or pulmonary eosinophilia. An analysis of TCR Vbeta chain usage confirmed a bias toward Vbeta14 expression on CD4(+) T cells from vvGs-immunized mice, whereas the CD4(+) T cells in FI-RSV-immunized mice expressed a diverse array of Vbeta chains. These data show that although FI-RSV and vvGs induce responses resulting in similar immunopathology, the T-cell repertoire mediating the response is different for each immunogen and suggest that the immune responses elicited by RSV G are not the basis for FI-RSV vaccine-enhanced disease.
Johnson
Teresa R
TR
Vaccine Research Center, NIAID, NIH, Bldg. 40, Room 2614, 40 Convent Dr., MSC 3017, Bethesda, MD 20892-3017, USA. teresaj@nih.gov
Varga
Steven M
SM
Braciale
Thomas J
TJ
Graham
Barney S
BS
D000818:Animals; D005557:Formaldehyde; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000503:physiopathology* / Q000517:prevention & control; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D014764:Viral Proteins; D005557:Formaldehyde