T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura

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Abstract

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disease, characterized by isolated thrombocytopenia and the absence of megakaryocytes in bone marrow. Recent studies suggest that this syndrome is due to diverse etiologies. Humoral or cellular mediated suppression has been alternately demonstrated using an in vitro colony assay for megakaryocytic progenitor cells (colony forming units megakaryocyte, [CFU-meg]). We studied a patient affected by AATP, who was not responsive to conventional therapy, but did respond to antilymphocyte globulin. The immunological characterization of marrow lymphocytes showed a marked increase of T activated suppressor cells (CD8+/DR+). Low density bone marrow mononuclear nonadherent cells (MNAC) from the patient, either in aplastic phase or in remission phase, were plated in plasma clot either directly or after T cell depletion (T-dep MNACs). Co-cultures with normal marrow cells were performed using either T lymphocytes from a normal volunteer donor or patient T lymphocytes. In some experiments we added autologous serum instead of fetal calf serum (FCS). In standard conditions, we observed increased colony formation, which was more evident in remission phase and especially significant after T cell depletion. The T lymphocytes from patient marrow did not modify the number of CFU-meg when co-cultured with allogeneic cells. These results indicate that an immune-mediated mechanism could be responsible for this case of AATP, and that the T cell subset CD8+/DR+ is capable of exerting suppression on megakaryocyte differentiation. This suppressive effect seems restricted to patient cells, suggesting a specific auto-sensitization.

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