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Influence of HLA-DRB1 alleles on Th1 and Th2 cytokine response to Mycobacterium tuberculosis antigens in pulmonary tuberculosis

Selvaraj, P and Rajeswari, D Nisha and Jawahar, M S and Narayanan, P R (2007) Influence of HLA-DRB1 alleles on Th1 and Th2 cytokine response to Mycobacterium tuberculosis antigens in pulmonary tuberculosis. Tuberculosis, 87 (6). pp. 544-550. ISSN Print:1472-9792; Online: 1873-281X

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Abstract

The influence of human leukocyte antigens (HLA) on the immune response is well established. We investigated the regulatory role of HLA-DRB1 alleles on cytokine response to live M. tuberculosis and its culture filtrate antigen (CFA) in normal healthy subjects (NHS) and pulmonary tuberculosis (PTB) patients. Th1 (IFN-g and IL-12p40), Th2 (IL-4 and IL-5), pro-inflammatory (IL-6 and IL-8) and anti-inflammatory (TGF-b and IL-10) cytokines were measured by ELISA in 72-h-old peripheral blood mononuclear cell culture supernatants from 58 NHS and 48 PTB patients. HLA-DRB1 genotyping was carried out by polymerase chain reaction and dot-blot hybridization with biotinylated sequence-specific oligonucleotide probes and detection by chemiluminescence. In response to live M. tuberculosis and CFA, significantly increased levels of IL-6, IL-8 and TGF-b and decreased IFN-g, IL-12p40 and IL-10 were seen in PTB patients compared to NHS. We observed a significantly increased IFN-g response in HLA-DRB1*03-positive NHS (p ¼ 0.03) and decreased IFN-g response in HLA-DRB1*15-positive patients (p ¼ 0.04) than respective allele-negative individuals. An increased level of IL-12p40 in DRB1*10 (p ¼ 0.02) and IL-10 in DRB1*12- (p ¼ 0.03) positive NHS and an increased level of IL-6 in DRB1*04- (p ¼ 0.02) positive patients were observed. The study suggests that HLA-DRB1 alleles differentially modulate the various cytokine responses to M. tuberculosis antigens, which may influence the cellular and humoral immune responses to M. tuberculosis infection in a susceptible host.

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Item Type: Article
Uncontrolled Keywords: HLA-DRB1 alleles; Cytokines; Pulmonary tuberculosis
Subjects: Tuberculosis > Laboratory Research > Immunological
Divisions: Basic Science Research > Immunology
Depositing User: Dr. Rathinasabapati R
Date Deposited: 09 Jan 2014 11:18
Last Modified: 09 Mar 2016 04:52
URI: http://eprints.nirt.res.in/id/eprint/828

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