Rv2626c and Rv2032 activate TH1 response and downregulate regulatory T cells in peripheral blood mononuclear cells of tuberculosis patients.

In the present study we have assessed T cell immuno-phenotypes in BCG vaccinated healthy individuals and patients with active pulmonary tuberculosis in response to two latency associated DosR Regulon Proteins Rv2626c and Rv2032. The proteins were shortlisted based on our previous bioinformatics analysis of the 48 DosR Regulon proteins. Both the proteins were seen to increase the percentage of CD4 and CD8 memory T cells in patients. Increase in expression of transcription factor T-Bet in response to the proteins suggested that the DosR proteins could be skewing the immune response toward the immune-protective TH1 type. This was confirmed with cell culture supernatant studies for release of TH1 and TH2 cytokines IFN- γ, IL-2, TGF-β, IL-4 and IL-10. A significant increase in frequency of CD4/IFN-γ and CD8/IFN-γT cells in patients was observed in response to both our proteins. This was accompanied with a significant downregulation in regulatory T cell population. Based on our findings of increase in TH1 response and decrease in Treg cells responsible for suppressing the immunity, we project Rv2626c and Rv2032 as antigens capable of inducing a strong immune response against Mycobacterium tuberculosis.