Is cytopenia in some patients with myelodysplastic syndrome (MDS) associated with the autoaggressive activity of T-cells?

R Neuwirtová MD PhD a, V Cukrová PhD b

a 1st Med Clin, Dept Clin Hematol, Charles University Hospital, Prague, Czech Republic b Inst Hematol Blood Transf, Prague, Czech Republic

INTRODUCTION: Certain MDS patients benefit from the immunosuppressive therapy with ATG or cyclosporin A .Both drugs suppress T-lymphocytes. There is some indirect evidence for the autoaggressive activity of T-cells against hematopoiesis in MDS. Apoptosis inducing cytokines, produced by T-cells ( TNF alfa, FasL and IFN gamma) are elevated in MDS bone marrow (BM). The number of colonies increases in BM cultures depleted by T-cells or due to the addition of anti TNF alfa-antibody. According to our results cocultivation of BM cells with TRAIL (member of TNF family) inhibits the colony formation. In more than half of 59 MDS patients an increased percentage of CD8 cells was found in the blood. Cytopenia observed in our 16 large granular lymphocytes leukemia patients resembles cytopenias in MDS; both cytopenias might be in connection with an increased FasL in both entities. AIM: We try to find out a direct evidence for autoaggressive activity of T-cells in MDS. METHOD: We developed a modified method of limiting dilution analysis of autoreactive cytotoxic T-cells. The assay consists in incubation of effector cells (PBMNC - peripheral blood mononuclear cells) with 51Cr labeled BMMNC and in analysis of 51Cr release. RESULTS: We demonstrated the presence of cytotoxic T-lymphocytes destroying autologous bone marrow targets in 3 of 5 patients tested. The search for the autoreactive T-cells in our MDS patients continues. CONCLUSION: Our preliminary results bring direct evidence for the existence of autoimmune mechanisms in the pathogenesis of MDS cytopenia mediated by cytotoxic T-lymphocytes.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Autoimmunity.