In Situ Expression of CD40, CD40L (CD154), IL-12, TNF-a, IFN-g and TGF-b1 in Murine Lungs during Slowly Progressive Primary Tuberculosis

Abstract

The distribution and expression of CD40, its ligand CD40L (154) and related cytokines interleukin-12 (IL-12), tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1) were studied in the lungs of B6D2F1 hybrid mice during slowly progressive primary tuberculosis (TB) by immunohistochemistry. CD40 and CD40L are implicated in cell-mediated immunity (CMI) causing activation or apoptosis of infected cells. The phenomenon of apoptosis is associated with Mycobacterium tuberculosis survival. In this study, using frozen lung sections (n = 33), our results showed increased CD40, IL-12 and TGF-β1 expression in macrophages with progression of disease. High percentages of mycobacterial antigens (M.Ags), CD40L and IFN-γ expression were maintained throughout infection, and TNF-α-expressing cells were decreased. In lymphocytes, the percentage of IFN-γ-positive cells was increased, but CD40L and IL-12 were maintained with the progression of disease. M.Ags, CD40 and CD40L were expressed in the same areas of the lesions. We conclude that changes in the expression of CD40–CD40L and cytokines associated with M. tuberculosis infection favour the hypothesis that M. tuberculosis causes resistance of host cells to apoptosis causing perpetuation of infection.