| Identification of human T-cell responses to Mycobacterium tuberculosis resuscitation-promoting factors in long-term latently infected individuals. | |
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MedLine Citation:
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PMID: 21248154 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Mycobacterium bovis BCG vaccine is the only tuberculosis (TB) vaccine available, yet it provides limited protection against pulmonary TB in adults and fails to protect against TB reactivation. We hypothesized that immunity against Mycobacterium tuberculosis "resuscitation-promoting factors" (Rpfs), which are small bacterial proteins that promote proliferation of dormant mycobacteria, may be relevant in the human immune response to M. tuberculosis. In previous unpublished work, we found that Rpfs Rv0867c and Rv2389c induced gamma interferon (IFN-γ) production in the blood of TB patients' healthy household contacts in several different African populations. Here we examine these two dominant Rpf antigens in more detail and define the nature of the responding T-cell subsets. Multiparameter cytokine profiling showed that Rv2389c and, to a lesser extent, Rv0867c were recognized by mycobacterium-responsive healthy Dutch individuals; peptide-scanning revealed several epitopes, including a single immunodominant epitope in Rv2389c. Rv0867c and, to a lesser extent, Rv2389c Rpf-specific T-cell responses were maintained for decades in long-term M. tuberculosis nonprogressors. Prominent Rv0867c-specific double- and single-cytokine-producing CD8(+) T-cell subset responses were found, including a large population of CD8(+) effector memory and effector T-cell subsets. We conclude that M. tuberculosis Rpf antigens are important targets in the human immune response to M. tuberculosis and represent interesting TB vaccine candidate antigens. |
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Authors:
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Susanna Commandeur; Krista E van Meijgaarden; May Young Lin; Kees L M C Franken; Annemieke H Friggen; Jan Wouter Drijfhout; Fredrik Oftung; Gro Ellen Korsvold; Annemieke Geluk; Tom H M Ottenhoff |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-01-19 |
Journal Detail:
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Title: Clinical and vaccine immunology : CVI Volume: 18 ISSN: 1556-679X ISO Abbreviation: Clin. Vaccine Immunol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-08 Completed Date: 2011-07-25 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 101252125 Medline TA: Clin Vaccine Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 676-83 Citation Subset: IM |
Affiliation:
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Department of Infectious Diseases, Leiden University Medical Center, Leiden 2333 ZA, Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Bacterial Proteins / immunology* Cytokines / immunology*, secretion Epitope Mapping Epitopes, T-Lymphocyte / immunology Humans Latent Tuberculosis / immunology* Mycobacterium tuberculosis / immunology* Netherlands T-Lymphocyte Subsets / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Cytokines; 0/Epitopes, T-Lymphocyte; 0/resuscitation-promoting factor, bacteria |
| Comments/Corrections | |
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