Abstract
BackgroundStudies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that Mycobacterium tuberculosis can actively interfere with the apoptosis of infected cells. In vivo studies have been performed in adult populations but have not focused on this process in children. In the present study, we analyzed spontaneous T lymphocyte (PBT) apoptosis in the peripheral blood of children with central nervous system tuberculosis (CNS TB), before and after chemotherapy, and compared the results with healthy controls.MethodsA case-control study was conducted from January 2002 to June 2009. It included 18 children with CNS TB and 17 healthy controls. Spontaneous apoptosis of PBTs, including CD4+, CD8+ and CD8+/CD28+ T cells, was evaluated after 24 and 72 h of culture in complete medium, using the Annexin V detection test. Analysis was conducted before and after chemotherapy, and expression of the apoptotic markers CD95 (Fas) and Fas ligand (FasL) was evaluated.ResultsHigher percentages of apoptotic T cells and CD4 lymphocytes were isolated from children with acute phase CNS TB than from children in the control group (p < 0.05). This difference significantly decreased after 60 days of specific treatment. In children with CNS TB, high levels of Fas ligand expression were detected in lymphocyte populations, associated with a high percentage of Fas positive cells, before and after treatment. In contrast to the CD4+ apoptosis profile, we did not find any significant difference in total CD8+ cell apoptosis between children with acute phase disease and the control group. However, the percentage of apoptotic CD8+/CD28+ T cells was significantly higher in the children with acute phase disease than in the healthy controls.ConclusionsOur findings indicate that CNS TB in pediatric patients increases the sensitivity of CD4 and CD8+/CD28+ T cells to apoptosis, suggesting a hypoergic status of this infection. This could play a key role in the immunopathogenesis of this complicated form of TB. Interestingly, specific chemotherapy is able to normalize both apoptosis sensitivity and T-cell activation.
Highlights
Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that Mycobacterium tuberculosis can actively interfere with the apoptosis of infected cells
Spontaneous apoptosis of PBTs isolated from central nervous system tuberculosis (CNS TB) patients and from the healthy controls was evident after 24 h (p < 0.0005), and steadily increased after 72 h (p < 0.0005)
Comparative analysis of apoptosis in CD8+ lymphocyte populations in acute phase central nervous system (CNS) TB children treated for 30-60 days and for more than 90 days and in the controls showed no significant differences after 24 and 72 h of incubation (p > 0.05)
Summary
Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that Mycobacterium tuberculosis can actively interfere with the apoptosis of infected cells. While 90% of immunocompetent adult patients infected by the tubercle bacillus will not develop the disease during their lifetime, children have shown various clinical forms of infection and progressive disease [2,3]. Pulmonary TB tends to be the most common form of TB, TB of the central nervous system (CNS) carries the highest mortality and morbidity rates and develops in 4% of infected children, especially during infancy [4,5,6]. Some progress towards understanding the mechanism involved in immune responses to Mycobacterium tuberculosis infection has been made by studying adult patients. The relevant role of apoptosis (programmed cell death) in the development of the immune system in children has recently been highlighted in studies on the efficacy of the TB vaccine [7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
