High levels of intracellular IL-4 are expressed in circulating apoptotic T cells in patients with tuberculosis and in community controls

SummaryData 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-4high). A larger subset of both CD4 and CD8 T cells of all subjects expressed low levels of intracellular IL-4 (IL-4low). Stimulated and unstimulated cells expressed IL-4low and IL-4high. IL-4low percentages were lower in TB patients at diagnosis compared to controls while IL-4high percentages were higher in patients. Most IL-4high 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.