Mycobacterial antigen-induced T helper type 1 (Th1) and Th2 reactivity of peripheral blood mononuclear cells from diabetic and non-diabetic tuberculosis patients and Mycobacterium bovis bacilli Calmette-Guérin (BCG)-vaccinated healthy subjects

• Published in: Clinical and experimental immunology Vol. 158; no. 1; pp. 64 - 73
• Main Authors: Al-Attiyah, R.J, Mustafa, A.S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2009; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Adult; analysis; Analytical, structural and metabolic biochemistry; Antigens, Bacterial; Antigens, Bacterial - pharmacology; Bacterial diseases; BCG Vaccine; Biological and medical sciences; Biomarkers; Biomarkers - analysis; Cell Proliferation; Cell Proliferation - drug effects; Cells, Cultured; complications; diabetes; Diabetes Mellitus; Diabetes Mellitus - immunology; Diabetes Mellitus - microbiology; Diabetes. Impaired glucose tolerance; Disease Susceptibility; drug effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Humans; Immunization; immunology; Infectious diseases; Interferon-gamma; Interferon-gamma - analysis; Interleukin-10; Interleukin-10 - analysis; Interleukin-2; Interleukin-2 - analysis; Lymphotoxin-alpha; Lymphotoxin-alpha - analysis; Male; Medical sciences; microbiology; Middle Aged; mononuclear leukocytes; Mycobacterium bovis; Mycobacterium bovis - immunology; peripheral blood mononuclear cells; pharmacology; prevention & control; T-Lymphocytes; T-Lymphocytes - immunology; Th1 and Th2 cytokines; Th1 Cells; Th1 Cells - immunology; Th2 Cells; Th2 Cells - immunology; Translational Studies; tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pulmonary; Tuberculosis, Pulmonary - complications; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - prevention & control; Young Adult; Endocrinopathy; Th1 lymphocyte; Biochemistry; Mycobacterial infection; Mononuclear cell; T-Lymphocyte; Bacteria; Th2 lymphocyte; Human; peripheral blood mononuclear cells; Healthy subject; Mycobacterium bovis; Th1 and Th2 cytokines; Diabetes mellitus; BCG; Cytokine; Infection; Antigen; Blood cell; Reactivity; Tuberculosis; Mycobacteriales; Bacteriosis; Mycobacteriaceae; Actinomycetes; diabetes
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.04000.x

Patients with diabetes mellitus are more susceptible to tuberculosis (TB), and the clinical conditions of diabetic TB patients deteriorate faster than non-diabetic TB patients, but the immunological basis for this phenomenon is not understood clearly. Given the role of cell-mediated immunity (CMI) in providing protection against TB, we investigated whether CMI responses in diabetic TB patients are compromised. Peripheral blood mononuclear cells (PBMC) obtained from diabetic TB patients, non-diabetic TB patients and Mycobacterium bovis bacilli Calmette-Guérin (BCG)-vaccinated healthy subjects were cultured in the presence of complex mycobacterial antigens and pools of M. tuberculosis regions of difference (RD)1, RD4, RD6 and RD10 peptides. The PBMC were assessed for antigen-induced cell proliferation and secretion of T helper 1 (Th1) [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-β], and Th2 (IL-4, IL-5, IL-10) cytokines as CMI parameters. All the complex mycobacterial antigens and RD1pool stimulated strong proliferation of PBMC of all groups, except moderate responses to RD1pool in healthy subjects. In response to complex mycobacterial antigens, both IFN-γ and TNF-β were secreted by PBMC of all groups whereas diabetic TB patients secreted IL-10 with concentrations higher than the other two groups. Furthermore, in response to RD peptides, IFN-γ and IL-10 were secreted by PBMC of diabetic TB patients only. The analyses of data in relation to relative cytokine concentrations showed that diabetic TB patients had lower Th1 : Th2 cytokines ratios, and a higher Th2 bias. The results demonstrate a shift towards Th2 bias in diabetic TB patients which may explain, at least in part, a faster deterioration in their clinical conditions.