Lymphocyte apoptosis in children with central nervous system tuberculosis

Background Progress in our understanding of the apoptosis mechanisms involved in the pathogenesis of tuberculosis suggests 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 the process in children. In the present study, we analyze spontaneous T-lymphocyte (PBT) apoptosis in the peripheral blood of children with Central Nervous System tuberculosis, before and after chemotherapy, and compare the results with healthy controls. Methods A 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 h and 72 h of culture in complete medium, using the Annexin V detection test. Analysis was conducted before and after chemotherapy, and apoptotic markers CD95 (Fas) and Fas ligand (FasL) expression were evaluated. Results Higher percentages of apoptotic T-cells and CD4 lymphocytes were isolated from children with acute phase CNS TB than from the children in the control group. The difference between the two groups decreased significantly after 60 days of specific treatment. As regards the illness group, high levels of Fas ligand expression were detected on lymphocyte populations, associated with a high percentage of Fas positive cells, before and after treatment. Contrary to the CD4+ apoptosis profile, we did not find any significant difference in total CD8 + cell apoptosis between the illness and control groups, whereas percentage of apoptotic CD8 + /CD28 + T cells was significantly higher in the children with acute phase disease than in the healthy controls. Conclusions Our findings indicate that CNS tuberculosis in pediatric patients increases the sensitivity of CD4 and CD8 + /CD28 + T cells to apoptosis, suggesting a hypoergic status in this infection. This could play a key role in the immunopathogenesis of this complicated form of TB. It is interesting that specific chemotherapy was able to normalize both apoptosis sensitivity and Tcell activation.