PURPOSE: Substantial cell mediated immune response is observed in patients infected with tuberculosis. The inadequacy of that response for elimination of bacteria may be partially at the level of modulated function of effector T cells. Regulatory T cells are likely to be involved critically in the immunopathogenesis of tuberculosis by influencing the effector immune response. Difference in the frequency of these regulatory cells in patients with tuberculosis may influence their status of immune response resulting in varied clinical manifestations. In this study we intend to investigate the representation of regulatory T cell subset(s) in patients with tuberculosis.
METHODS: To study the frequency of Regulatory T cells (CD4+CD25+Foxp3+) in tuberculosis patients FACS based staining (surface staining for CD4 & CD25 whereas intranuclear staining for Foxp3) was performed. In addition reverse transcriptase PCR was also performed to detect Foxp3 expression at mRNA level.Magnetic sorting methods & Cell Proliferation assay were also performed.
RESULTS: To evaluate the representation of Treg in TB patients we studied 15 TB pleural effusion and 10 Miliary TB (MTB) patients for their representation in peripheral blood and selective enrichment at the local disease site(s) namely pleural effusion and bronchoalveolar lavages(BAL). Controls included healthy subjects and few malignant pleural effusion cases as disease controls. It was observed that though activated T cells (CD4+CD25+) were overrepresented in tubercular pleural effusion over MTB, the frequency of Treg cells (CD4+CD25+Foxp3+) was significantly higher at local disease sites in Miliary TB in comparison to that of tuberculous pleural effusion. FoxP3 mRNA levels were significantly higher in BALs obtained from MTB, as compare to peripheral blood. In addition Treg cells obtained from BAL were found to suppress the proliferation of PBMCs.
CONCLUSION: These results highlight the importance of Treg cells in suppression of Th1-like protective immune response, thereby influencing the disease manifestation and severity.
CLINICAL IMPLICATIONS: This hints towards the potential of Treg cells for therapeutic implications to fine tune the protective effector immune response in infectious diseases like tuberculosis.
DISCLOSURE: Prabhat Sharma, None.