Premature senescence of T lymphocytes from patients with beta-thalassemia major.
Several researches have demonstrated a suppressed cell mediated immunity in patients with beta-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 beta-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 24h incubation in medium. Flow cytometric data revealed that lymphocytes from beta-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 beta-thalassemia major; possibly result in abnormal T cell function leading to suppressed cell mediated immunity.
Gharagozloo
Marjan
M
Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran. gharagozlo@sums.ac.ir
Bagherpour
Bahram
B
Tahanian
Mahmoud
M
Oreizy
Farzad
F
Amirghofran
Zahra
Z
Sadeghi
Hamid Mir Mohammad
HM
Hourfar
Hamid
H
Moayedi
Behjat
B
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens; D016827:CD8 Antigens; D002469:Cell Separation; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D019014:fas Receptor; D019098:Telomerase