HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, W. Articles by Arulanandam, B. P. Search for Related Content PubMed PubMed Citation Articles by Li, W. Articles by Arulanandam, B. P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Chlamydia Infections Vaginal Diseases

Antigen-Specific CD4⁺ T Cells Produce Sufficient IFN- to Mediate Robust Protective Immunity against Genital Chlamydia muridarum Infection¹

Weidang Li^2,*, Ashlesh K. Murthy^2,*, M. Neal Guentzel^*, J. Seshu^*, Thomas G. Forsthuber^*, Guangming Zhong and Bernard P. Arulanandam^3,*

^* Department of Biology, South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, TX 78249; and Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229

Chlamydia has been shown to evade host-specific IFN--mediated bacterial killing; however, IFN--deficient mice exhibit suboptimal 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- or the IFN- receptor for intranasal vaccination with a defined secreted chlamydial Ag, chlamydial protease-like activity factor (CPAF), plus CpG and examined the role of IFN- derived from adoptively transferred Ag-specific CD4⁺ T cells in protective immunity against genital C. muridarum infection. We found that early Ag-specific IFN- induction and CD4⁺ T cell infiltration correlates with the onset of genital chlamydial clearance. Adoptively transferred IFN- competent CPAF-specific CD4⁺ T cells failed to enhance the resolution of genital chlamydial infection within recipient IFN- receptor-deficient mice. Conversely, IFN- production from adoptively transferred CPAF-specific CD4⁺ T cells was sufficient in IFN--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- signaling and that such cells produce sufficient IFN- 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- production for effective protective immunity against human genital chlamydial infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant SO6GM008194-24.

² W.L. and A.K.M. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Bernard Arulanandam, Department of Biology, University of Texas, One UTSA Circle, San Antonio, TX 78249. E-mail address: Bernard.arulanandam{at}utsa.edu

⁴ Abbreviations used in this paper: CPAF, chlamydial protease-like activity factor; MHC I/II, MHC class I/II; i.n., intranasal; HEL, hen egg lysozyme; IFU, inclusion-forming unit; i.vag., intravaginal(ly).

Related articles in The JI:

IN THIS ISSUE

The JI 2008 180: 2721-2722. [Full Text]