title: High levels of intracellular IL-4 are expressed in circulating apoptotic T cells in patients with tuberculosis and in community controls.
abstract: Data concerning T helper cell phenotypes in response to Mycobacterium tuberculosis infection remain controversial. T lymphocyte intracellular interleukin-4 production in response to CD3 stimulation was determined by flow cytometry in 21 TB patients and 14 community controls. In supplementary experiments the association of interleukin-4 expression with apoptosis was investigated. A low percentage of CD4 T cells in both patients and controls expressed high levels of interleukin-4 (IL-4(high)). A larger subset of both CD4 and CD8 T cells of all subjects expressed low levels of intracellular IL-4 (IL-4(low)). Stimulated and unstimulated cells expressed IL-4(low) and IL-4(high). IL-4(low) percentages were lower in TB patients at diagnosis compared to controls while IL-4(high) percentages were higher in patients. Most IL-4(high) cells co-expressed active caspase-3, a marker for apoptosis. This co-expression was also shown in experimentally induced apoptotic Jurkat cells and peripheral blood neutrophils and monocytes. IL-4 levels may therefore not necessarily indicate a skewed Th cell phenotype, as our data suggest that IL-4 production by CD4 and CD8 T cells can occur constitutively in healthy controls with latent TB infection and in TB patients. Cellular IL-4 production may represent a normal cellular growth factor mechanism which is disturbed at the onset of apoptosis.
authors.affiliation: Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, South Africa. hveen@sun.ac.za
authors.forename: Hanne
authors.initials: H
authors.lastname: Veenstra
authors.forename: Ralf
authors.initials: R
authors.lastname: Baumann
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Lukey
authors.forename: Nulda
authors.initials: N
authors.lastname: Beyers
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis*; D019169:Jurkat Cells; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D009169:Mycobacterium tuberculosis; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D053148:Caspase 3