Nat Med. 2011 Mar;17(3):372-6. Epub 2011 Feb 20.

Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease.

Harari A, Rozot V, Enders FB, Perreau M, Stalder JM, Nicod LP, Cavassini M, Calandra T, Blanchet CL, Jaton K, Faouzi M, Day CL, Hanekom WA, Bart PA, Pantaleo G.

Source

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

Abstract

Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4+ T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4+ T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4+ T cells is a new tool for the rapid diagnosis of active tuberculosis disease.

PMID:: 21336285; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances

Publication Types

Research Support, Non-U.S. Gov't

MeSH Terms

Substances

Tumor Necrosis Factor-alpha

LinkOut - more resources

Full Text Sources

Other Literature Sources

See the articles identified as outstanding by F1000's Faculty of 10,000 renowned researchers and clinicians. - F1000

Medical

Tuberculosis - MedlinePlus Health Information

Supplemental Content

Save items

Related citations in PubMed

Double- and monofunctional CD4⁺ and CD8⁺ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals. [Eur J Immunol. 2011]
Double- and monofunctional CD4⁺ and CD8⁺ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals.
Commandeur S, Lin MY, van Meijgaarden KE, Friggen AH, Franken KL, Drijfhout JW, Korsvold GE, Oftung F, Geluk A, Ottenhoff TH. Eur J Immunol. 2011 Oct; 41(10):2925-36. Epub 2011 Aug 30.
Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons. [J Infect Dis. 2008]
Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons.
Day CL, Mkhwanazi N, Reddy S, Mncube Z, van der Stok M, Klenerman P, Walker BD. J Infect Dis. 2008 Apr 1; 197(7):990-9.
T cells co-producing Mycobacterium tuberculosis-specific type 1 cytokines for the diagnosis of latent tuberculosis. [Eur Cytokine Netw. 2010]
T cells co-producing Mycobacterium tuberculosis-specific type 1 cytokines for the diagnosis of latent tuberculosis.
Nemeth J, Winkler HM, Karlhofer F, Selenko-Gebauer N, Graninger W, Winkler S. Eur Cytokine Netw. 2010 Mar; 21(1):34-9.
Review [Evolution of IGRA researches]. [Kekkaku. 2008]
Review [Evolution of IGRA researches].
Ariga H, Harada N. Kekkaku. 2008 Sep; 83(9):641-52.
Review Reactivation of tuberculosis by tumor necrosis factor neutralization. [Eur Cytokine Netw. 2007]
Review Reactivation of tuberculosis by tumor necrosis factor neutralization.
Jacobs M, Samarina A, Grivennikov S, Botha T, Allie N, Fremond C, Togbe D, Vasseur V, Rose S, Erard F, et al. Eur Cytokine Netw. 2007 Mar; 18(1):5-13. Epub 2007 Mar 30.

See reviews... See all...

Cited by 10 PubMed Central articles

Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations. [Tuberc Res Treat. 2011]
Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations.
Ariga H, Nagai H, Kurashima A, Hoshino Y, Shoji S, Nakajima Y. Tuberc Res Treat. 2011; 2011:940642. Epub 2011 Jun 27.
Distinct Effector Memory CD4(+) T Cell Signatures in Latent Mycobacterium tuberculosis Infection, BCG Vaccination and Clinically Resolved Tuberculosis. [PLoS One. 2012]
Distinct Effector Memory CD4(+) T Cell Signatures in Latent Mycobacterium tuberculosis Infection, BCG Vaccination and Clinically Resolved Tuberculosis.
Adekambi T, Ibegbu CC, Kalokhe AS, Yu T, Ray SM, Rengarajan J. PLoS One. 2012; 7(4):e36046. Epub 2012 Apr 24.
Peripheral T cell cytokine responses for diagnosis of active tuberculosis. [PLoS One. 2012]
Peripheral T cell cytokine responses for diagnosis of active tuberculosis.
Nemeth J, Winkler HM, Zwick RH, Müller C, Rumetshofer R, Boeck L, Burghuber OC, Winkler S. PLoS One. 2012; 7(4):e35290. Epub 2012 Apr 16.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discri...
Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease.
Nat Med. 2011 Mar ;17(3):372-6. Epub 2011 Feb 20 .

PubMed
Association of a functional variant downstream of TNFAIP3 with systemic lupus er...
Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus.
Nat Genet. 2011 Mar ;43(3):253-8. Epub 2011 Feb 20 .

PubMed
Structural basis for allosteric regulation of human ribonucleotide reductase by ...
Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization.
Nat Struct Mol Biol. 2011 Mar ;18(3):316-22. Epub 2011 Feb 20 .

PubMed
Dynamics of Sir3 spreading in budding yeast: secondary recruitment sites and euc...
Dynamics of Sir3 spreading in budding yeast: secondary recruitment sites and euchromatic localization.
EMBO J. 2011 Mar 16 ;30(6):1012-26. Epub 2011 Feb 18 .

PubMed
Carotenoids and their isomers: color pigments in fruits and vegetables.
Carotenoids and their isomers: color pigments in fruits and vegetables.
Molecules. 2011 Feb 18 ;16(2):1710-38.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: