Abnormal Polarization of T Lymphocyte in Myelodysplastic Syndrome Marrow and Its Negtative Effect on Hematopoiesis.

Abstract

Objective: To explore polarization of T lymphocyte and its relationship with apoptosis of marrow cells in patients with myelodysplastic syndromes (MDS).Methods: Measurement of Th1, Th2, Tc1, Tc2 subsets of marrows from 35 patients with MDS and 13 normal controls was performed by flow cytometry. INF-γ and TNF-α in the bone marrow serum were tested by ELISA (Enzyme-linked immunosorbent assay). Furthermore, apoptosis index of marrow cells was detected by TUNEL (TdT-mediated dUTP nick end labeling). Correlation among Th1, Th2, Tc1, Tc2 subsets and INF-γ, TNF-α level as well as apoptosis index were analyzed, and relationship between TNF-α, INF-γ level and apoptosis index was also investigated.Results:The percentage of Th1 cells (10.1±1.5%), Tc1 cells (24.2±3.5%) and Tc1/Tc2 ratio (49.7±10.8) was significantly increased in patients with MDS when compared to normal controls (4.0±0.5%, 5.8±0.6% and 13.4±2.7, respectively). Level of INF-γ (57.4±21.9pg/ml) and TNF-α (14.6±3.7pg/ml) in bone marrow serum of patients with MDS was markedly elevated compared to normal controls (0 and 0.3±0.2pg/ml, respectively). An increased apoptosis index of nucleated cells was also observed in patients with MDS (7.2±1.5%) when compared to controls (2.1±0.3%, P<0.05). The Th1 cells percentage showed a positive correlation with level of INF-γ and TNF-α (r=0.38, P<0.05 and r=0.39, P<0.05, respectively), and also a positive correlation with apoptotic index of nucleated marrow cells in patients with MDS (r=0.33, P<0.05). Furthermore, a positive correlation was observed when the relationship between INF-γ, TNF-α level and apoptotic index of marrow cells were analyzed (r=0.74, P<0.01 and r=0.73, P<0.01, respectively).Th1, Tc1 cells and Tc1/Tc2 ratio in patients with RCMD (according to WHO classification) was markedly elevated (P<0.01) while not significantly increased in patients with RCMD-RS, RAEB-1 and RAEB-2 when compared to normal controls.An elevation in the percentage of Th1 (11.1±1.9%), Tc1 (25.1±3.8%) and Tc1/Tc2 ratio (58.6±15.8%) was detected in patients with lower-risk (defined by IPSS), while there was no difference between higher-risk group and controls.Conclusions: Th1/Th2, Tc1/Tc2 in bone marrow of patients with MDS were unbalanced, which were polarized to typeIreaction especially in patients with RCMD subtype and lower-risk group. The increased Th1 cells in marrow may account for apoptosis of nucleated marrow cells in MDS, which may act through proapoptotic cytokines such as INF-γ and TNF-α.