Deviation of type I and type II T cells and its negative effect on hematopoiesis in myelodysplastic syndrome

Immunemediated hematopoietic suppression has been considered as one of significant pathophysiological changes in less-advanced myelodysplastic syndrome (MDS). To explore deviation of T cell subsets and its relationship to marrow cells apoptosis, measurement of helper-T (Th)/cytotoxic-T (Tc) subsets as well as the deviation situation within this two subsets (Th1/Th2 and Tc1/Tc2) in marrow was performed by flow cytometry from 39 MDS patients and 13 normal controls. Interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha in marrow serum was simultaneously detected by ELISA (enzyme-linked immunosorbent assay). Furthermore, apoptosis rate of marrow cells was demonstrated by TUNEL (TdT-mediated dUTP nick end labeling). Results showed that Th and Tc subsets were unevenly activated, both deviating to type I response, which was especially obvious in patients with RCMD (according to WHO classification) and in lower-risk cases defined by International Prognosis Scoring System (IPSS). Level of INF-gamma/TNF-alpha in MDS marrow serum was markedly elevated, and so did the apoptosis rate of marrow cells. Although type I deviation was observed both in Th and Tc subsets, just Th1 cell percentage showed positive correlation with level of INF-gamma/TNF-alpha and apoptotic index of nucleated cells. In addition, cytokines level in marrow serum presented positive correlation to apoptosis. We then deduced that the increased Th1 cells in marrow may account for nucleated cells apoptosis in MDS through overproduced proapoptotic cytokines such as INF-gamma and TNF-alpha. Our results suggested that type I deviation of T cell subsets may play a role in pantocytopenia in MDS and the deviation pattern may be as a direct and effective parameter to predict response of immunosuppression therapy.