Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein (Vac-M2) is mediated by CD8+ T cells, while that induced by Vac-F or Vac-G recombinants is mediated by antibodies.
It was previously demonstrated that the vaccinia virus recombinants expressing the respiratory syncytial virus (RSV) F, G, or M2 (also designated as 22K) protein (Vac-F, Vac-G, or Vac-M2, respectively) induced almost complete resistance to RSV challenge in BALB/c mice. In the present study, we sought to identify the humoral and/or cellular mediators of this resistance. Mice were immunized by infection with a single recombinant vaccinia virus and were subsequently given a monoclonal antibody directed against CD4+ or CD8+ T cells or gamma interferon (IFN-gamma) to cause depletion of effector T cells or IFN-gamma, respectively, at the time of RSV challenge (10 days after immunization). Mice immunized with Vac-F or Vac-G were completely or almost completely resistant to RSV challenge after depletion of both CD4+ and CD8+ T cells prior to challenge, indicating that these cells were not required at the time of virus challenge for expression of resistance to RSV infection induced by the recombinants. In contrast, the high level of protection of mice immunized with Vac-M2 was completely abrogated by depletion of CD8+ T cells, whereas depletion of CD4+ T cells or IFN-gamma resulted in intermediate levels of resistance. These results demonstrate that antibodies are sufficient to mediate the resistance to RSV induced by the F and G proteins, whereas the resistance induced by the M2 protein is mediated primarily by CD8+ T cells, with CD4+ T cells and IFN-gamma also contributing to resistance.
Connors
M
M
Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Kulkarni
A B
AB
Collins
P L
PL
Firestone
C Y
CY
Holmes
K L
KL
Morse
H C
HC
Murphy
B R
BR
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D005260:Female; D015707:HN Protein; D006801:Humans; D007114:Immunization; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G