Lymphocyte apoptosis in children with central nervous system tuberculosis: a case control study

• Main Authors: Carlo Paola Di, Casuccio Alessandra, Romano Amelia, Spicola Daria, Titone Lucina, Caccamo Nadia, Dieli Francesco, Mammina Caterina, Pace Elisabetta, Gjomarkaj Mark, Melis Mario, Tolomeo Manlio
• Format: Article
• Language: English
• Published: BMC 2011-11-01
• Series: BMC Pediatrics
• Online Access: http://www.biomedcentral.com/1471-2431/11/108

<p>Abstract</p> <p>Background</p> <p>Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that <it>Mycobacterium tuberculosis </it>can actively interfere with the apoptosis of infected cells. <it>In vivo </it>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.</p> <p>Methods</p> <p>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 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.</p> <p>Results</p> <p>Higher 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.</p> <p>Conclusions</p> <p>Our 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.</p>