Evaluation of T cell immune responses in multi-drug-resistant tuberculosis (MDR-TB) patients to Mycobacterium tuberculosis total lipid antigens

• Published in: Clinical and experimental immunology 2007-08, Vol.149 (2), p.285-294
• Main Authors: Shahemabadi, A.S, Hosseini, A. Zavaran, Shaghsempour, S, Masjedi, M.R, Rayani, M, Pouramiri, M
• Format: Article
• Language: English
• Subjects: Adult; Analytical, structural and metabolic biochemistry; Antigens, Bacterial - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Electrophoresis, Polyacrylamide Gel - methods; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunity, Cellular; interferon-gamma; Interferon-gamma - biosynthesis; interleukin-4; Interleukin-4 - biosynthesis; Lipids - immunology; Male; Middle Aged; Molecular biophysics; multi-drug-resistant tuberculosis; Mycobacterium tuberculosis; T cells; T-Lymphocyte Subsets - immunology; T-lymphocytes; total lipid antigens; Translational Studies; Tuberculin - immunology; Tuberculin Test; Tuberculosis, Multidrug-Resistant - immunology
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2007.03406.x

Mycobacterium tuberculosis lipid antigens produce significant T cell responses in healthy tuberculin reactor [purified protein derivative (PPD-positive] individuals. In the present study, proliferation and interferon (IFN)-γ/interleukin (IL)-4 responses were analysed to M. tuberculosis total lipid antigens in T lymphocytes from 25 patients with multi-drug-resistant tuberculosis (MDR-TB). The obtained results were compared with those of 30 asymptomatic healthy PPD-positive and 30 healthy tuberculin skin test negative (PPD-negative) subjects. Peripheral blood mononuclear cells (PBMCs) and T cells (CD4⁺ and CD8⁺) were stimulated using autologous immature dendritic cells. Proliferation responses were assessed using 3-{4,5-dimethylthiazol-2-yl}-2,5 diphenyl tetrazolium bromide (MTT). IFN-γ/IL-4 concentrations in the supernatant of the CD4⁺ and CD8⁺T cells were measured by enzyme-linked immunosorbent assay. Proliferation assay showed that the peripheral blood mononuclear cells and CD4⁺ T cells from the MDR-TB patients responded significantly less to the M. tuberculosis total lipid antigens than to the CD4⁺ T cells in the PPD-positive subjects. Total lipid antigen-specific proliferative responses in the CD8⁺ T cells from the MDR-TB patients were minimally detected and the responses were similar to those of the PPD-positive subjects. IFN-γ production by the CD4⁺ T cells stimulated by total lipid antigens from the MDR-TB patients was decreased significantly compared with the PPD-positive individuals, whereas IL-4 production in the patients was elevated. IFN-γ and IL-4 production in the CD8⁺ T cells of the MDR-TB patients was similar to those of the PPD-positive subjects. In conclusion, it is suggested that stimulated CD4⁺ T cells by M. tuberculosis total lipid antigens may be shifted to T helper 2 responses in MDR-TB patients.