Background: Tuberculosis remains a serious public health threat worldwide. It has been estimated that 2 billion people worldwide are latently infected with Mycobacterium tuberculosis. A vast pool of individuals with latent tuberculosis infection (LTBI) persists in developing countries, posing a major barrier to global TB control. Immunosuppressive regulatory T-cells (T-Regs) and CD4+ T-lymphocytes in general are important in the host immune response to LTBI. T-Regs down regulate the immune system to prevent excessive immune responses which may eventually lead to autoimmune disease and immunopathology. Activated T-Regs on the other hand, as they limit host immunity they can inhibit pathogen clearance hence facilitating pathogen multiplication and dissemination. However, their role in the regulation of Latent TB infection (LTBI) in household contacts is not yet fully defined.
Methods: This was a retrospective cross sectional study. Household contacts of adult smear positive TB patients in Kampala, Uganda were enrolled and investigated for LTBI using Tuberculin Skin Test (TST) and QuantiFERON ®-TB Gold In-Tube (QFN). LTBI was defined as a positive result of both TST and QFN. Cryo-preserved peripheral blood mononuclear cells (PBMCs) were used to determine the number and phenotypic markers of T-Regs among household contacts (HHC) with or without LTBI using multi-color flow cytometry. The difference between the two groups was compared using the Mann Whitney test for non-parametric tests.
Results: The study analyzed samples from 18 HHC with LTBI and 22 HHC without LTBI and found that the natural (naïve) T-Regs were increased in the HHC with no LTBI (median 70 cells, (Inter-quartile range (IQR) 25) as compared to HHCs with LTBI (60 cells (IQR) 18), (P=0.0278). On the other hand, the induced (memory) T-Regs were higher in HHC with LTBI (median 40 cells, (IQR) 18.2) than those without LTBI (median 30 cells, (IQR) 25), (P=0.0045). In the Phenotypic analysis, the natural T-Regs were CD4+CD127low/-CD45RO– while the induced T-Regs were CD4+ CD127low/-CD45RO+ as expected.
Conclusions: These results suggest that there is a relationship between T-Regs and TB latency. It is anticipated that the MTB antigenic persistence in the individuals with LTBI induces a continuous generation of T-Regs resulting from the rapid turnover of induced T-Regs increasing their number in this select population. Further studies are needed to access for the function of these raised T-Regs.