CD4+ T cells are required during priming but not the effector phase of antibody-mediated IFN-gamma-dependent protective immunity against pulmonary Francisella novicida infection.
We have previously demonstrated the protective efficacy of intranasal vaccination with a defined Francisella tularensis subsp. novicida DeltaiglC mutant (KKF24) against pulmonary F. novicida U112 challenge. In this study, we further characterized the mechanisms of KKF24-induced immunity. Intranasally vaccinated KKF24 C57BL/6 major histocompatibility class (MHC) class II-/- mice produced minimal antigen-specific interferon (IFN)-gamma and serum antibodies and were highly susceptible (0% survival) to F. novicida challenge, compared to MHC class I-/- or wild-type mice (both 100% survival). Protective immunity could be transferred by immune serum into recipient wild type, but not IFN-gamma-/- mice. The protective effect of KKF24 vaccination against the respiratory F. novicida U112 challenge was not abrogated by anti-CD4 neutralizing antibody treatment and was not conferred by adoptive transfer of KKF24-specific CD4+ T cells. The protective effect of antibody was partially dependent upon Fc receptor-mediated clearance. Taken together, our data indicate that CD4+ T cells are required for priming, but not during the effector phase, of anti-KKF24 antibody-mediated IFN-gamma-dependent immunity against pulmonary F. novicida infection.
Powell
Heather J
HJ
Department of Biology, South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Cong
Yu
Y
Yu
Jieh-Juen
JJ
Guentzel
M Neal
MN
Berton
Michael T
MT
Klose
Karl E
KE
Murthy
Ashlesh K
AK
Arulanandam
Bernard P
BP
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005604:Francisella tularensis / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology*; D008168:Lung / Q000382:microbiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015996:Survival Rate; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control*; D014611:Vaccination
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; C485701:Fcgr1 protein, mouse; C485700:Fcgr3 protein, mouse; D017452:Receptors, IgG; D007371:Interferon-gamma