title: Effect of 1,25 dihydroxyvitamin D3 on intracellular IFN-gamma and TNF-alpha positive T cell subsets in pulmonary tuberculosis.
abstract: We studied the immunomodulatory effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha cytokines in T cell subsets of pulmonary tuberculosis (PTB) patients (n=22) and normal healthy subjects (n=22). Peripheral blood mononuclear cells (PBMCs) were cultured with live Mycobacterium tuberculosis (MTB) with or without 1,25(OH)(2)D(3) (10(-7)M) for 48 h. T cell subsets positive for IFN-gamma and TNF-alpha were enumerated by flow cytometry and the culture supernatants were assayed for both the cytokines using ELISA. In both NHS and PTB patients, a significantly reduced percentage of IFN-gamma and TNF-alpha expressing CD3+, CD3+CD4+ and CD3+CD8+ T cells were observed in cultures stimulated with live MTB and treated with 1,25(OH)(2)D(3) compared to cultures without 1,25(OH)(2)D(3) (NHS; CD3+ IFN-gamma+: p<0.0001; CD3+TNF-alpha+: p=0.0292 and PTB; CD3+ IFN-gamma+: p=0.0292; CD3+ TNF-alpha+: p=0.0028). The levels of IFN-gamma and TNF-alpha in the culture supernatants of 1,25(OH)(2)D(3) treated cultures were also found to be significantly decreased in both groups (NHS; IFN-gamma: p=0.0001; TNF-alpha: p<0.0001) and (PTB; IFN-gamma: p<0.0001; TNF-alpha: p<0.0001). A positive correlation was observed between IFN-gamma and TNF-alpha expressing CD3+CD8+ T cells in MTB stimulated cultures treated with or without 1,25(OH)(2)D(3) in NHS (p=0.0001; p=0.001, respectively) and PTB patients (p=0.002; p=0.005, respectively). The present study revealed the suppressive effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha by CD3+CD4+ and CD3+CD8+ T cells in pulmonary tuberculosis. This suppressive effect of 1,25(OH)(2)D(3) on proinflammatory and Th1 cytokine positive cells might have a role in reducing inflammation at the site of infection.
authors.affiliation: Department of Immunology, Tuberculosis Research Centre, Indian Council of Medical Research, Mayor V.R. Ramanathan Road, Chennai 600 031, Tamil Nadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Prabhu Anand
authors.forename: P
authors.initials: P
authors.lastname: Selvaraj
authors.forename: P R
authors.initials: PR
authors.lastname: Narayanan
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002117:Calcitriol