Defective cytotoxicity of T lymphocytes in myelodysplastic syndrome

The capacity of mononuclear blood cells to form autoreactive cytotoxic T lymphocytes was investigated in order to elucidate the mechanism of successful immunosuppressive therapy in some myelodysplastic syndrome (MDS) patients (autoreactivity studies). The failure in autoreactivity studies raised the question of alloreactive cytotoxic T lymphocyte formation in MDS (alloreactivity studies).

Sixteen MDS patients and relevant controls were examined. Autoreactive lymphocytes directed against autologous bone marrow mononuclear cells and alloreactive lymphocytes directed against unrelated third-party cells were tested using cytotoxicity assay. In addition, we used one-way mixed lymphocyte reaction, human androgen receptor test for clonality detection, and enzyme-linked immunosorbent assay kits for tumor necrosis factor and interferon-gamma testing.

We did not confirm the presence of autoreactive T cells in eight of nine MDS patients tested. The response to allogeneic cells was impaired in 11 of 16 MDS patients, more often in refractory anemia (RA; 80%) than in RA with ring sideroblasts (40%). Interestingly, the response to allogeneic cells in mixed lymphocyte reaction was normal in all MDS patients. T lymphocytes were polyclonal in all but one patient. Tumor necrosis factor and interferon-gamma level in supernatants of mononuclear cells was significantly reduced in RA.

The presumed autoaggressive T cells were not confirmed in MDS in our experimental arrangement. Alloreactivity studies demonstrated the impairment of effector cytotoxic phase of cell-mediated immunological reaction in MDS, namely in RA. The significance of our finding of defective cytotoxicity for pathogenesis, clinical course, and even for therapy is discussed together with other immunological defects reported so far.