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J Infect. 2013 Jun;66(6):475-86. doi: 10.1016/j.jinf.2013.02.004. Epub 2013 Feb 24.

IFNγ/TNFα specific-cells and effector memory phenotype associate with active tuberculosis.

Author information

1
Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.

Abstract

OBJECTIVES:

Controversial results were reported on the role of polyfunctional T-cells in tuberculosis (TB). Our aim was to simultaneously characterize the Mycobacterium tuberculosis (Mtb)-specific immune response as cytokine production and memory phenotype by flow cytometry after in vitro stimulation with region of difference 1 ("RD1") recombinant proteins (ESAT-6 and CFP-10) in patients at different TB stage in a low TB endemic country. To assess the specificity of these findings, we evaluated the response to cytomegalovirus (CMV), an unrelated antigen.

METHODS:

We enrolled subjects with active TB, cured TB, latent TB infection (LTBI). Cytokine and phenotype profiles of T-cells from whole blood stimulated with "RD1" proteins and CMV were characterized by multi-parametric flow cytometry.

RESULTS:

Bifunctional IFNγ(+) TNFα(+) CD4(+) T-cells and effector memory phenotype significantly associated with active TB compared to the LTBI group (p = 0.008, at least p ≤ 0.009 respectively) whereas "RD1"-T-cell response in cured TB and LTBI was characterized by a central memory phenotype (at least p ≤ 0.013 and p ≤ 0.004 respectively vs active TB). In contrast, response to CMV antigen was not associated with a TB-specific status.

CONCLUSION:

We identified qualitative associations between Mtb-specific T-cell and TB status in terms of functional capacity and memory status. These immune correlates may be helpful to trace natural history of TB.

PMID:
23462597
DOI:
10.1016/j.jinf.2013.02.004
[Indexed for MEDLINE]

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