Inhibiting HLA-G restores IFN-γ and TNF-α producing T cell in pleural Tuberculosis. (March 2018)

• Record Type: Journal Article
• Authors: Saurabh, Abhinav; Chakraborty, Sushmita; Kumar, Prabin; Mohan, Anant; Bhatnagar, Anuj K.; Rishi, Narayan; Mitra, Dipendra Kumar
• Is Part Of: Tuberculosis. Volume 109(2018)
• Page Start: 69
• Page End: 79
• Publication Date: 2018-03
• Subjects: HLA-G -- Tuberculosis Pleural Effusion (TB-PE) -- Pro-inflammatory cytokines; HLA-G Human Leukocyte Antigen-G -- TB-PE Tuberculosis Pleural Effusion -- IL Interleukin -- ADA Adenosine Deaminase -- ILT Immunoglobulin-like Transcript -- KIR Killer cell Immunoglobulin-like receptor; 616.995
• DOI: 10.1016/j.tube.2018.01.008
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Human Leukocyte Antigen-G (HLA-G), a non-classical, class Ib molecule, has been shown to mediate immunoregulatory functions by inducing apoptosis, inhibits cytotoxicity and differentiation by modulating cytokine secretion. Due to its immune-suppressive function, it facilitates tolerance in feto-maternal interface and transplantation. In contrary, it favours immune evasion of microbes and tumors by inhibiting immune and inflammatory responses. In Tuberculosis (TB), we previously reported differential expression of HLA-G and its receptor Ig-like transcript −2 (ILT-2) in disseminated vs. localized Tuberculosis. The present study explores the impact of HLA-G inhibition on the function of T cells and monocytes, in TB Pleural Effusion (PE), a localized form of TB. Blocking of HLA-G resulted in significant increase in IFN-γ and TNF-α production by CD3 + T cells. Additionally, we observed that HLA-G influences the apoptosis and cytotoxic effect of T cells from TB- PE patients. Next, we checked the impact of interaction between HLA-G and ILT-4 receptor in monocytes derived from TB-PE patients upon blocking and observed significant increase in IFN-γ production. The present study reveals for the first time HLA-G mediated suppression of Th1 cytokines, especially, IFN-γ and TNF-α in TB-PE patients.