Immune Suppression by Regulatory T Cells in Human Tuberculosis

Abstract

Tuberculosis has co-evolved along-with humans and as such continues to be a scourge of humanity. However, various factors that can disrupt M.tb latency leading to the emergence of active TB are intriguing and now a research of immense importance. HLA-G is reported to possess potent immuno-suppressive capability and its role has been evaluated in different pathological/tolerogenic environments such as Cancer, HIV, transplantation, etc. newlineOur observation of increased soluble HLA-G in Miliary TB relative to TB-PE suggests of its role in contributing to the immuno-suppressed state and dissemination of MTB. MMPs have also been shown to contribute towards lung cavities in TB. The present work sheds a new light on HLA-G mediated up-regulation of Fas expressing T cells especially in MTB in comparison to TB-PE. Further evaluation of recombinant HLA-G mediated apoptosis of T cells producing IFN-and#947; indicates association of Fas - Fas-L pathway in MTB. This work sheds light on the differential mode of suppression of immune response among TB-PE and MTB patients. TB-PE, representing an immuno-reactive form of TB showed suppression in terms of preferential inhibition of Th1 cytokine production; whereas, MTB, representing immuno-suppressive form of TB, showed suppression in terms of apoptosis of effector T cells. Further research may reveal whether HLA-G can also inhibit bystander T cells similar to HIV-1 positive progressors. To the best our knowledge, this may be the first study demonstrating differential protein expression and functions of both soluble and cell surface HLA-G in two different spectrums of TB disease. We presume that evaluation of BALF of Miliary TB patients for HLA-G1/G5 could help in delineating their role on interaction between DCs and CD4+ T cells. Additionally, studying a larger cohort of TB patients and their follow-up during anti-tubercular therapy will further helpin discerning the immunology of HLA-G in tuberculosis. newline newline