FoxP3+ regulatory T cells suppress effector T cell function at pathologic site in miliary tuberculosis

Abstract

Rationale: The inadequacy of effector T cell response in containment of tubercle bacilli is thought to result in the development of disseminated forms of tuberculosis (TB) such as miliary tuberculosis (MTB). Regulatory T cells (Treg) plausibly play a critical role in the immunopathogenesis of disseminated TB by suppression of effector immune response against M. tuberculosis at the pathologic site(s). To understand the role of Treg cells in disseminated tuberculosis, we studied the frequency and function of Treg cells derived from the local disease site specimens (LDSS) of patients with TB pleural effusion and MTB as clinical models of contained and disseminated forms of disease, respectively. Objectives: We aimed at (i) Enumerating the frequency of Treg cells in bronchoalveolar lavage (BAL) fluid of patients suffering from MTB and comparing with that of peripheral blood (ii) Studying the role of Treg cells in suppression of local T cell response and (iii) their selective recruitment at the local disease site(s). Methods: Flow cytometry, reverse transcriptase PCR and MTT based cell proliferation assay. Results: Frequency of Treg cells (CD4⁺CD25⁺Foxp3⁺) was significantly higher at LDSS in MTB along with higher levels of FoxP3 mRNA. Importantly, FoxP3⁺ Treg cells obtained from the BAL of MTB patients predominantly produced IL-10 and could suppress the autologous T cell proliferation in response to M. tuberculosis antigen. Conclusions: Our results highlight the importance of Treg cells in suppression of effector immune response and their influence on the bacillary dissemination, disease manifestation and severity.