Pulmonary Tuberculosis: Decreased Activation of T lymphocyte Subsets in vitro

Protection against M. tuberculosis depends on T cells of the CD4(+) or CD8(+) phenotype. The definition of cellular response and target molecules are important to understand pathological immune mechanisms in tuberculosis. In this report we have analyzed the expression of activation markers (CD25, CD71, HLA DR) on CD4(+), CD8(+) subsets in patients with pulmonary tuberculosis by dual color flow cytometry. We investigated 19 patients with newly diagnosed severe active untreated pulmonary tuberculosis. Previously it was shown, that in the above form of pulmonary tuberculosis amidst CD4(+) and CD8(+) T cells there were a significant decrease in quantity of CD45RA(+) lymphocytes and increase in CD25(+), HLA DR(+) activated cells. To estimate the functional significance of these differences, peripheral blood mononuclear cells were stimulated with polyclonal mitogen phytoheamaglutin in vitro. Since the decreased mitogen response could reflect a difference in the ability of T cell subsets to proliferate, the phenotype of the T cells after stimulation with PHA was determined. Although the patients with PT demonstrated a decreased number of all the T cell subsets (CD25(+), CD71(+), HLA DR(+) after 72 h of PHA-stimulation compared to control, the most pronounced decrease was in CD8(+) cells. Differential analysis of the activation markers in dependence on the flow cytometry gates for PHA-stimulated lymphocytes revealed some defect in the expression of activation markers at the level of small blasts that arrested CD4(+), CD8(+) cells on the early activation stages. Taken together these results suggest that investigated clinical form of pulmonary tuberculosis seems to be directly associated with a defect in reactivity of T lymphocyte subsets at the early activation steps.