Role Of T-bet In The Pathogenesis Of Aplastic Anemia

Objective: To measure the quantity, proportion of Th1 and Th2 cells in peripheral blood, the subsets of T lymphocyte and the quantity of CD8+HLA-DR+ cells in bone marrow , and the expression of T-bet and GATA-3 mRNA in bone marrow mononuclear cells(BMMNC) of aplastic anemia(AA); evaluate the relationships between the T-bet and Th1 cells, CD3+CD8+ cells, CD8+HLA-DR+ cells or hematopoietic funtion and explore the role of T-bet and Th1 cells in the pathogenesis of AA. Methods: ①The quantity of the subsets of T lymphocyte and CD8+HLA-DR+ cells in bone marrow of AA patients at diagnosis and normal controls were detected respectively by FACS.②Th1 and Th2 cells in peripheral blood mononuclear cells(PBMNC) of AA patients and normal controls were counted by FACS.③mRNA expression of T-bet and GATA-3 gene in unstimulated BMMNC from AA patients and normal controls were measured by reverse transcriptase polymerase chain reaction(RT-PCR). Results: ①In aplastic anemia patients, bone marrow,the percentage of CD3+CD4+ cells,CD3+CD8+cells,CD8+HLA-DR+cells and the ratio of CD4+/CD8+ were (35.05±9.47)%,(36.29±6.81)%,(18.36±2.07)% and 1.0±0.33 respectively.In normal controls,they were (52.84±4.03)%, (24.69±3.90)%, (11.13±1.14)% and 2.14±0.24 respectively.The percentage of CD3+CD4+ cells and the ratio of CD4+/CD8+ of AA patients were significantly lower than that of controls;the percentage of CD3+CD8+ cells and CD8+HLA-DR+ cells were significantly higher than that of controls;whirle the percentage of CD3+cells, CD19+ cells and CD16+CD56+cells had no difference between AA patients and normal controls. ②The percentage of Th1 cells and the ratio of Th1/Th2 of AA patients were significantly higher than that of controls,the percentage of Th2 cells had no difference between AA patients and normal controls.③The positive rates of T-bet and GATA-3 of AA patients were 17/20 and 14/20.In normal controls,they were 2/15 and 3/15.Moreover the expression intensity of T-bet was higher in AA patients than the normal controls.④The percentage of Th1 cells in AA patients were positively correlated with their CD3+CD8+ cells and CD8+HLA-DR+ cells,and negatively correlated with their RC and ANC.AA patients, T-bet expression were positively correlated with their Th1 cells and CD3+CD8+ cells,but negatively with their RC and ANC. Conclusions: Predominant expression of T-bet in AA patients might promote Th0 cells to polarize to Th1 cells, cause the over-function of Th1 cells, increased the activity and numbers of CD3+CD8+ cells, overproduction of inhibitory hematopoietic cytokines and hematopoiesis failure.