Study On The Mechanisms Of Hematopoiesis Damage By Effector T Cells Of The Patients With Severe Aplastic Anemia

Objective:To investigate the quantity and function of effector T cells subsets of patients with severe aplastic anemia(SAA) and explore the immunopathoge-nisis of SAA further.Methods:The quantity of CD8+CD25+and CD8+HLA-DR+cells in PB and their expression of perforin, granzyme B, tumor necrosis factor-β(TNF-β) and FasL of 14 untreated SAA patients,15 remitted SAA patients and 12 healthy controls were analyzed by flow cytometry.Results:1. The variations of effective T cell①The ratio of CD8+CD25+T cells in CD8+T cells was (3.67±2.58)% in untreated SAA group and there was no statistical difference between SAA and controls [(4.84±2.31)%] (P>0.05).The ratio of CD8+CD25+T cells in CD3+T cells was (2.25±1.35)% and there was no statistical difference between SAA and controls [(2.11±1.88)%] (P>0.05).The ratio of CD8+HLA-DR+T cells in CD8+T cells was (39.30±8.13)% in SAA untreated group,which was higher than cintrols [(18.34±6.68)%] (P>0.05).The ratio of CD8+HLA-DR+T cells in CD3+T cells was (27.81±7.10)%,which was significantly higher than that of controls [(8.50±2.33) %] (p<0.01)②The ratio of CD8+CD25+T cells in CD8+T cells was (5.19±4.29)% in remitted SAA patients, and there was no statistical difference between SAA and controls [(4.84±2.31)%] (P>0.05).The ratio of CD8+CD25+T cells in CD3+T cells was (2.98±1.35)% and there was no statistical difference between SAA and controls [(2.11±1.88)%] (P>0.05).The ratio of CD8+HLA-DR+T cells in CD8+T cells was (20.65±5.38)% in SAA remitted group,and there was no statistical difference between SAA and controls[(18.34±6.68)%](P>0.05). The ratio of CD8+HLA-DR+T cells in CD3+T cells was (12.02±3.03)%,which was higher than that of controls [(8.50±2.33)%] (p<0.05)③The ratio of CD8+CD25+T cells in CD8+T cells was (3.67±2.58)% in untreated SAA group and there was no statistical difference between SAA untreated patients and remitted group [(5.19±4.29)%] (P>0.05).The ratio of CD8+CD25+T cells in CD3+T cells was (2.25±1.35)% and there was no statistical difference between SAA untreated patients and remitted group [(2.98±1.35)%] (P>0.05). The ratio of CD8+HLA-DR+T cells in CD8+T cells was (39.30±8.13)% in SAA untreated group,which was significant higher than remitted group [(20.65±5.38)%] (p<0.001).The ratio of CD8+HLA-DR+T cells in CD3+T cells was (27.81±7.10) %,which was significantly higher than that of remitted group [(12.02±3.03)%] (p<0.01)2. The variations of expression of perforin granzyme B TNF-P and FasL①The median expression of perforin and granzyme B of CD8+CD25+ cells were 35.42% and 93.21% in untreated SAA group,and there were no statistical differences between SAA and controls (23.34%,68.34%) (p>0.05). The median expression of TNF-βand FasL were 100.00% and 100.00%, which were significantly higher than controls (56.85%,50.00%) (p<0.05), The expressions of perforin, granzyme B, TNF-βand FasL of CD8+HLA-DR+T cells in SAA untreated group were 8.51%. 96.08%.72.11% and 94.25% respectively, those were higher than those of control group (1.86%,82.09%.17.92%.32.91%) (p<0.05)②The median expression of perforin and granzyme B of CD8+CD25+ cells were 7.69% and 9.20% in remitted group,and there were no statistical differences between SAA and controls (23.34%,68.34%) (p>0.05). The median expression of TNF-βand FasL were 54% and 65%, and there were no statistical defference between SAA and controls (56.85%,50.00%) (p>0.05), The expressions of perforin,granzyme B, TNF-βand FasL of CD8+HLA-DR+T cells in SAA untreated group were 1.78%. 85.20%.34.38%. and 51.20% respectively, and there were no statistical defference between SAA and controls (1.86%.82.09%.17.92%.32.91%) (p>0.05)Conclusion:The quantity and function of CD8+HLA-DR+T cells in SAA were higher than that in controls. Perforatin, granzyme B, TNF-βand FasL may be the main pathway in hematopoietic cell apoptosis induced by effective T cells.