Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile

Chlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic...

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Published in:	Clinical and vaccine immunology Vol. 22; no. 11; pp. 1206 - 1218
Main Authors:	Picard, Michele D, Bodmer, Jean-Luc, Gierahn, Todd M, Lee, Alexander, Price, Jessica, Cohane, Kenya, Clemens, Veronica, DeVault, Victoria L, Gurok, Galina, Kohberger, Robert, Higgins, Darren E, Siber, George R, Flechtner, Jessica Baker, Geisler, William M
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 01-11-2015
Subjects:	Adolescent Adult Antibodies, Bacterial - immunology Antigens, Bacterial - immunology CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Chlamydia Infections - immunology Chlamydia Infections - microbiology Chlamydia trachomatis Chlamydia trachomatis - genetics Chlamydia trachomatis - immunology Epitopes, T-Lymphocyte - immunology Female Humans Immunity, Cellular Interferon-gamma - immunology Male Middle Aged Proteomics Reproductive Tract Infections - immunology Reproductive Tract Infections - microbiology Vaccines Young Adult
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Summary:	Chlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI). The human immune response against C. trachomatis, an obligate intracellular bacterium, is poorly characterized but is thought to rely on cell-mediated immunity, with CD4(+) and CD8(+) T cells implicated in protection. In this report, we present immune profiling data of subjects enrolled in a multicenter study of C. trachomatis genital infection. CD4(+) and CD8(+) T cells from subjects grouped into disease-specific cohorts were screened using a C. trachomatis proteomic library to identify the antigen specificities of recall T cell responses after natural exposure by measuring interferon gamma (IFN-γ) levels. We identified specific T cell responses associated with the resolution of infection, including unique antigens identified in subjects who spontaneously cleared infection and different antigens associated with C. trachomatis-related sequelae, such as TFI. These data suggest that novel and unique C. trachomatis T cell antigens identified in individuals with effective immune responses can be considered as targets for vaccine development, and by excluding antigens associated with deleterious sequelae, immune-mediated pathologies may be circumvented.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 M.D.P. and J.-L.B. contributed equally to this work. Deceased. Citation Picard MD, Bodmer J-L, Gierahn TM, Lee A, Price J, Cohane K, Clemens V, DeVault VL, Gurok G, Kohberger R, Higgins DE, Siber GR, Flechtner JB, Geisler WM. 2015. Resolution of Chlamydia trachomatis infection is associated with a distinct T cell response profile. Clin Vaccine Immunol 22:1206–1218. doi:10.1128/CVI.00247-15. Present address: Todd M. Gierahn, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Kenya Cohane, BioLegend, Inc., Dedham, Massachusetts, USA; Victoria L. DeVault, Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont, USA; Galina Gurok, George Washington University Law School, Washington, DC, USA.
ISSN:	1556-6811 1556-679X
DOI:	10.1128/CVI.00247-15