Diversity of lung and spleen immune responses in mice with slowly progressive primary tuberculosis

The aim of the present study was to assess the compartmentalized immune res ponse, in terms of cytokine secretion and cell activation, in lungs and spl eens of mice with slowly progressive primary tuberculosis. Immunocyte popul ations from both organs were isolated and stimulated with concanavalin A, p urified protein derivatives and MPT 59. Production of interferon-gamma (IFN -gamma) and interleukin-4 (IL-4) was measured using an enzyme-linked immuno sorbent assay, and cell activation was measured using a tetrazolium colorim etric assay. The IFN-gamma and IL-4 levels in the supernatants of Mycobacte rium tuberculosis antigen (Ag)-stimulated lung immunocytes from infected mi ce were higher than the levels from uninfected mice. However, only IL-4 lev els were raised in the supernatants of Ag-stimulated spleen immunocytes fro m infected mice. Spontaneous and Ag-stimulated immunocyte activation was lo wer only in the lungs of infected mice compared with uninfected mice. The l evel of lung immunocyte activation was inversely associated with the extent of gross pulmonary pathology. In conclusion, cytokine secretion and cell a ctivation were different between lungs and spleens in slowly progressive pr imary murine tuberculosis. Cytokine diversity may explain the confinement o f tuberculous lesions in the lungs and the absence of lesions in the spleen s of mice with slowly progressive tuberculosis.