CD4+ T cells are required during priming but not the effector phase of antibody-mediated IFN-γ-dependent protective immunity against pulmonary Francisella novicida infection

Heather J. Powell, Yu Cong, Jieh Juen Yu, M. Neal Guentzel, Michael T. Berton, Karl E. Klose, Ashlesh K. Murthy, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We have previously demonstrated the protective efficacy of intranasal vaccination with a defined Francisella tularensis subsp. novicida ΔiglC 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)-γ 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-γ-/- 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-γ-dependent immunity against pulmonary F. novicida infection.

Original languageEnglish (US)
Pages (from-to)515-522
Number of pages8
JournalImmunology and Cell Biology
Volume86
Issue number6
DOIs
StatePublished - Aug 2008

Keywords

  • Antibody
  • CD4 T cell
  • Fc receptor
  • Francisella tularensis
  • IFN-γ
  • MHC II

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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