Antigen-specific CD4+ T cells produce sufficient IFN-γ to mediate robust protective immunity against genital Chlamydia muridarum infection

Weidang Li, Ashlesh K. Murthy, M. Neal Guentzel, J. Seshu, Thomas G. Forsthuber, Guangming Zhong, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Chlamydia has been shown to evade host-specific IFN-γ-mediated bacterial killing; however, IFN-γ-deficient mice exhibit sub-optimal late phase vaginal Chlamydia muridarum clearance, greater dissemination, and oviduct pathology. These findings introduce constraints in understanding results from murine chlamydial vaccination studies in context of potential implications to humans. In this study, we used mice deficient in either IFN-γ or the IFN-γ receptor for intranasal vaccination with a defined secreted chlamydial Ag, chlamydial protease-like activity factor (CPAF), plus CpG and examined the role of IFN-γ derived from adoptively transferred Ag-specific CD4+ T cells in protective immunity against genital C. muridarum infection. We found that early Ag-specific IFN-γ induction and CD4 + T cell infiltration correlates with the onset of genital chlamydial clearance. Adoptively transferred IFN-γ competent CPAF-specific CD4 + T cells failed to enhance the resolution of genital chlamydial infection within recipient IFN-γ receptor-deficient mice. Conversely, IFN-γ production from adoptively transferred CPAF-specific CD4+ T cells was sufficient in IFN-γ-deficient mice to induce early resolution of infection and reduction of subsequent pathology. These results provide the first direct evidence that enhanced anti-C. muridarum protective immunity induced by Ag-specific CD4+ T cells is dependent upon IFN-γ signaling and that such cells produce sufficient IFN-γ to mediate the protective effects. Additionally, MHC class II pathway was sufficient for induction of robust protective anti-C. muridarum immunity. Thus, targeting soluble candidate Ags via MHC class II to CD4+ T cells may be a viable vaccine strategy to induce optimal IFN-γ production for effective protective immunity against human genital chlamydial infection.

Original languageEnglish (US)
Pages (from-to)3375-3382
Number of pages8
JournalJournal of Immunology
Volume180
Issue number5
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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