期刊
PLOS ONE
卷 7, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0043733
关键词
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资金
- CTRI RAMS
- National Institutes of Health grant [1RO1AI078899]
- Russian Foundation for Basic Research grant [10-04-01128]
- National Institute for Mathematical and Biological Synthesis [EF-0832858]
- University of Tennessee, Knoxville
- ISTC grant [4072]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0832858] Funding Source: National Science Foundation
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-gamma(+) cells). The percentages of CD27(low) IFN-gamma(+) 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-gamma(+) cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27(low) IFN-gamma(+) cells in blood was lung destruction (r = 0.65, p = 2.7x10(-7)). A cutoff of 47% of CD27(low) IFN-gamma(+) cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27(low) IFN-gamma(+) 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-gamma(+)) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27(low) IFN-gamma(+) 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-gamma(+) cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.
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