Premature senescence of T lymphocytes from patients with β-thalassemia major

Several researches have demonstrated a suppressed cell mediated immunity in patients with β-thalassemia major. To know whether the premature aging of T cells is involved in abnormalities of cell mediated immunity, the biomarkers of immunosenescence including telomerase activity, apoptosis, and the expression of CD28 and CD95 were evaluated in T lymphocytes from β-thalassemia major patients. The ex vivo spontaneous apoptosis in CD4+ or CD8+ T cells from patients and healthy subjects was assessed by an in situ TdT mediated dUTP-biotin nick end labelling (TUNEL) assay after 24 h incubation in medium. Flow cytometric data revealed that lymphocytes from β-thalassemia patients were resistant to spontaneous apoptosis compared to the normal lymphocytes. Moreover, the percentages of TUNEL+CD4+ or TUNEL+CD8+ T cells from patients were significantly lower than those control cells. Quantitative determination of telomerase activity in resting and activated T cells was performed using the Telomeric Repeat Amplification Protocol (TRAP). The results showed a decreased telomerase activity of activated T cells in patients with thalassemia major compared to that in healthy controls. However, the percentages of CD8+CD28− and CD3+CD95+ T lymphocytes were significantly higher in thalassemia patients, indicating the phenotypes associated with senescent T lymphocytes. These data provide evidences for the occurrence of accelerated aging of T cells in β-thalassemia major; possibly result in abnormal T cell function leading to suppressed cell mediated immunity.