CD4(+) T-cell-mediated antiviral protection of the upper respiratory tract in BALB/c mice following parenteral immunization with a recombinant respiratory syncytial virus G protein fragment.
We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4(+), but not CD8(+), T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967-1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4(+) T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection.
Plotnicky-Gilquin
H
H
Centre d'Immunologie Pierre Fabre, 74 164 St. Julien en Genevois, France. helene.plotnicky@pierre.fabre.com
Robert
A
A
Chevalet
L
L
Haeuw
J F
JF
Beck
A
A
Bonnefoy
J Y
JY
Brandt
C
C
Siegrist
C A
CA
Nguyen
T N
TN
Power
U F
UF
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015707:HN Protein; D007112:Immunity, Maternally-Acquired; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000517:prevention & control* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G