Research Of Subset And Function Of Th Cells In Bone Marrow Of Myelodysplastic Syndrome Patients

【OBJECTIVES】Myelodysplastic syndromes (MDS) are a group of malignant clonal haematopoietic stem cell diseases characterized by dysplasia haematopoiesis in one or three of the myeloid cell linages and high risk to convert to acute leukemia . Up to now there has no effective therapeutic measure for MDS. More and more evidences have been proved that the immune system of MDS patient is abnormal, and the abnormalty grows more serious with the development of the leukemic transition. All these hint that not only the qualitative alteration to carcinosis of the stem cell is related to the malignant haematopoiesis but also the abnormal immune system. Now there are two contra viewpoints : one considers that the immune function of the patient with MDS is in the phase of hypofunction ,it can not kill the malignant clone of MDS effectively , and this results in the transformation of the disease to acute leukemia; Another view is that the immune fuction of the patient suffering MDS is in the phase of accentuation , that increases the negative regulatory factors which depress the normal haemopoiesis and at last result in the bone marrow failure. Weather the immune system is in the accentuation or the inhibitory state? Our research is about the changes of the function and subset of CD4+ (Th) lymphocyte of the MDS patients which is much important for antitumorigenesis,it might help to reveal the immunopathogenesis and provide some cue for the immunotherapy of MDS. 【METHODS】By FACS, the quantity and ratio of IFN-γ producing CD4+ T cell (Th1) and IL-4 producing CD4+ T cell (Th2) cells in the bone marrow were detected in 21 patients with MDS, 18 normal controls and 13 patients with SAA respectively.The correlation between the ratio of the blast cells in the bone marrow and the number of the Th1 cells in the patients with MDS was analyzed. The karyotypes of 18 patients with MDS and15 normal controls were detected, The burden,(the number of the cells with anormal karyotypes /the number of all the detected cells) that Th1 cells bear in the patients with MDS and that in normal controls were also analyzed. 【RESULTS】The percentages of Th1 cells and Th2 cells and ratio of Th1/Th2 in the bone marrow of normal controls were: 0.48%,0.24% and 2.31％respectively , while those of the patients with MDS 0.36%,0.76% and 0.51 .The percentage of Th1 cells of patients with MDS was reduced and the ratio of Th1/Th2 of them was significantly lower than that of normal controls(P=0.008).Those of the patients with SAA were: 4.75％,0.40％,and 26.5 respectively , their Th1 cells and ratio of Th1/Th2 were markedly higher than those of normal controls (P﹤0.01). The lower ratio of the Th1 cells in the bone marrow of the patients with MDS and the AML which converts from MDS , the higher percentage of the blast cells, they were negatively correlated (r=－0.563, p<0.01).In all of the 15 normal controls the karyotypes were normal , and tumor cell burden was zero ; While in the group of MDS, tumor cell burden, (the number of the cells with anormal karyotype /the number of all detected cells) was 50% . The number of Th1 cells (0.36%)of the patients with MDS was lower than that of normal controls (0.48%),but the MDS patients' ratio of tumor cell burden / Th1 cells (1.72)was much higher than that of normal controls whose burden was zero.【CONCLUSIONS】The immune function of T lymphocytes in MDS is abnormal : the balance between Th1 and Th2 cells is broken . Th1 cell , the most important element for antitumorigenesis ,is decreased in quantity and weaken in function.With descending of the number of Th1 cells in the bone marrow of the patients with MDS , the number of the blast cells contrarily grows .Comparing with the burden of the malignant clone , the number of Th1 cells of the patients with MDS is overwhelmingly scarce. Myeloid hemopoietic clone of MDS has high tendency to convert to malignancy. MDS is a heterogeneous group of neoplastic disease accompanied with hypofunction of the T...