Mtb-specific CD27 low 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 lowIFN-γ +" cells). The percentages of CD27 lowIFN-γ+ 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 lowIFN-γ + cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27 lowIFN-γ + cells in blood was lung destruction (r = 0.65, p = 2.7×10 -7). A cutoff of 47% of CD27 lowIFN-γ + cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27 lowIFN-γ +cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Conclusions: Highly differentiated CD27 low Mtb-specific (CD27 lowIFN-γ +) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27 lowIFN-γ + 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 lowIFN-γ + cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy. © 2012 Nikitina et al.