Dataset Information

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

ABSTRACT:

Background

Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection.

Methodology/principal findings

The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27(low) cells within a population of Mtb- specific CD4 T lymphocytes ("CD27(low)IFN-?(+)" cells). The percentages of CD27(low)IFN-?+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27(low)IFN-?(+) cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27(low)IFN-?(+) cells in blood was lung destruction (r = 0.65, p = 2.7 × 10(-7)). A cutoff of 47% of CD27(low)IFN-?(+) cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27(low)IFN-?(+)cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01).

Conclusions

Highly differentiated CD27(low) Mtb-specific (CD27(low)IFN-?(+)) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27(low)IFN-?(+) cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27(low)IFN-?(+) cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.

SUBMITTER: Nikitina IY

PROVIDER: S-EPMC3427145 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

Nikitina Irina Yu IY Kondratuk Natalya A NA Kosmiadi George A GA Amansahedov Rasul B RB Vasilyeva Irina A IA Ganusov Vitaly V VV Lyadova Irina V IV

PloS one 20120824 8

<h4>Background</h4>Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T ...[more]

PMID: 22937086

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Project description:PurposeTo determine the diagnostic accuracy of the Xpert MTB/RIF assay in patients with smear-negative pulmonary tuberculosis (TB) and to assess clinical and CT characteristics of Xpert-negative pulmonary TB.Material and methodsWe retrospectively reviewed the records of 1,400 patients with suspected pulmonary TB for whom the sputum Xpert MTB/RIF assay was performed between September 1, 2014 and February 28, 2020. Clinical and CT characteristics of smear-negative pulmonary TB patients with negative Xpert MTB/RIF results were compared with positive results.ResultsOf 1,400 patients, 365 (26.1%) were diagnosed with pulmonary TB and 190 of 365 patients (52.1%) were negative for sputum acid-fast bacilli. The diagnosis of pulmonary TB was based on a positive culture, positive Xpert MTB/RIF or the clinical diagnoses of patients treated with an anti-TB medication. The sensitivity, specificity, positive predictive and negative predictive values of sputum Xpert MTB/RIF for smear-negative pulmonary TB were 41.1%, 100%, 100%, and 90.1%, respectively. Finally, 172 patients with smear-negative pulmonary TB who underwent chest CT within 2 weeks of diagnosis were included to compare Xpert-positive (n = 66) and Xpert- negative (n = 106) groups. Patients with sputum Xpert-negative TB showed lower positive rates for sputum culture (33.0% vs. 81.8%, p<0.001) and bronchoalveolar lavage culture (53.3% vs. 84.6%, p = 0.042) than in Xpert-positive TB. Time to start TB medication was longer in patients with Xpert-negative TB than in Xpert-positive TB (11.3±16.4 days vs. 5.0±8.7 days, p = 0.001). On chest CT, sputum Xpert-negative TB showed significantly lower frequency of consolidation (21.7% vs. 39.4%, p = 0.012), cavitation (23.6% vs. 37.9%, p = 0.045), more frequent peripheral location (50.9% vs. 21.2 p = 0.001) with lower area of involvement (4.3±4.3 vs. 7.6±6.4, p<0.001). Multivariate analysis revealed peripheral location (odds ratios, 2.565; 95% confidence interval: 1.157-5.687; p = 0.020) and higher total extent of the involved lobe (odds ratios, 0.928; 95% confidence interval: 0.865-0.995; p = 0.037) were significant factors associated with Xpert MTB/RIF-negative TB. Regardless of Xpert positivity, more than 80% of all cases were diagnosed of TB on chest CT by radiologists.ConclusionThe detection rate of sputum Xpert MTB/RIF assay was relatively low for smear negative pulmonary TB. Chest CT image interpretation may play an important role in early diagnosis and treatment of Xpert MTB/RIF-negative pulmonary TB.

Dataset Information

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

Background

Methodology/principal findings

Conclusions

Publications

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

Similar Datasets

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