Characterization of Circulating T Helper Cells in Post-tuberculosis Pulmonary Sequelae

Abstract Rationale: The outcome of Mycobacterium tuberculosis (Mtb) infection is largely determined by the host's immune response, specifically the nature and intensity of immune activation and inflammation. Although these immune mechanisms are essential for protecting the host against mycobacteria, excessive or unregulated immune responses can be detrimental, potentially worsening TB disease and leading to post-TB sequelae. T cells play a crucial role in controlling Mtb infection through immune activation and inflammation, but dysregulation in their response can contribute to tissue damage, potentially leading to both TB progression and post-TB sequelae. Methods: Patients having chronic anatomic and symptomatic sequelae arising from previously treated and microbiologically cured pulmonary tuberculosis (TB) (PTS, n=9; age=46.20±10.05) and healthy participants (HC, n=15; age=37.50±9.95 years) were recruited in this study. Flow Cytometry was performed on peripheral blood mononuclear cells to identify circulatory T cells with phenotypes: T helper type 1 (CD3+ CD4+ IFN-γ+); T helper type 2 (CD3+ CD4+ IL-4+) and T helper type 17 (CD3+ CD4+ IL-17A+)Results: The percentage of T helper type 1(CD3+ CD4+ IFN-γ+) was significantly lower in post tuberculosis sequelae patients as compared to healthy controls(13.15±8.22 Vs. 33.51±19.09; p-0.01). Post tuberculosis sequelae patients also show higher percentage of Th17 cells as compared to healthy controls [5.8(3.1-9) Vs. 0.75(0.42-5.72); p-0.035]. The percentage of T helper type 2(CD3+ CD4+ IL-4+) cells was significantly higher in post tuberculosis sequelae patients as compared to healthy controls [4.1(0.5-6.6) Vs. 0.2(0.1-0.52);p-0.0048]. Conclusion: These findings indicate that the activation of circulating T helper cell phenotypes may contribute to the pathogenesis of TB-associated pulmonary fibrosis. Th1 cells may contribute to post-tuberculosis sequelae by promoting a pro-inflammatory response. Th17 cells may contribute to persistent inflammation in post TB patients even after microbiological cure, while Th2 cells may promote fibrotic responses, potentially leading to structural lung changes.