Evidence for genetic restriction in the suppression of erythropoiesis by a unique subset of T lymphocytes in man.

Abstract

A B S T R A C T The suppression of erythropoiesis by lymphocytes from patients with a T cell lymphoproliferative syndrome and pure erythrocyte aplasia has been previously demonstrated. To study the nature of the suppressor cell and possible genetic restriction of this suppression, we investigated a patient with severe anemia, splenomegaly, lymphocytosis, and erythroid aplasia. A 3-mo course of low-dose daily oral cyclophosphamide achieved a complete remission for over 12 mo. The surface phenotype of his lymphocytes was analyzed by means of antibodies to lineage, differentiation, and activation-specific surface antigens. The cells expressed mature T cell antigens T3, T8, and Tll, while lacking Ti. Immature T cell, B cell, and the monocyte-specific antigen Mo2 were absent, while Mol, a monocyte-associated antigen not normally expressed on T cells, was present. T1O and Ia expressed as activation antigens were also present. The cells, cryopreserved at diagnosis, were thawed and co-cultured in plasma clot with patient remission marrow samples at T cell/bone marrow ratios of 1:1 and 2:1.There was nearly 90% suppression of erythroid colonyforming unit expression and 60% suppression of erythroid burst-forming unit expression at 2:1 T cell to bone marrow ratios and somewhat less suppression at 1:1. Granulocyte/macrophage progenitor expression was unaffected. Erythroid progenitor differentiation This work was presented in part at the 24th Annual Meeting of the American Society of Hematology, Washington, DC, 4-7 December 1982. Dr. Nadler was supported by a grant from the Medical Foundation of Boston.Received for publication 13 December 1982 and in revised form 20 April 1983. in the marrows of two HLA identical siblings was similarly suppressed. The cells were co-cultured with the marrows of nine nonrelated donors to investigate the potential genetic restriction of this suppression. Colony suppression equal to that observed in the marrow of the patient and his siblings was found in studies of two partially HLA identical individuals. No suppression was detected in marrow co-cultures of two entirely HLA dissimilar individuals. These results show that suppression of erythropoiesis by a unique subset of T8, Mol, Ia-positive lymphocytes isolated from a patient with lymphocytosis and erythrocyte aplasia is genetically restricted.

Abnormalities of myeloid progenitor cells after "successful" bone marrow transplantation.

“…Following marrow transplantation, the recipients hematopoietic cells are donorderived, genetically identical to the transplant donor. Similar evidence of immunologic restoration of T cell inhibition of hematopoiesis has been reported by others (17,18).…”

Inadequate Ability of T-Lymphocytes from Chronic Uremic Subjects to Stimulate the in vitro Growth of Committed Erythroid Progenitors (BFU-E)

“…In the present study in fact the MNC fraction containing the BFU-E was contaminated by 1-4% of monocytes, and the T-lymphocyte fraction consisted of about 1-2% of monocytes. Conflicting evidence is reported suggesting that normal blood T cells contain at least two functionally distinct subpopulations with opposing regulatory effects: OKT4+ T cells enhanc ing burst formation and OKT8+ T cells not pro ducing BPA or even suppressing erythroid growth un der specific conditions [9,10,12,27,30]. If the pro duction of BPA is restricted to one T cell subset or if erythropoiesis is regulated by two different T cell sub sets, variations in T cell subpopulations may then in fluence the differentiation and/or proliferation of BFU-E by altering the release and/or availability of BPA or even inhibiting BFU-E growth.…”

Pure Red Cell Aplasia Associated to Clonal CD8+ T-Cell Large Granular Lymphocytosis: Dependence on Cyclosporin A Therapy

“…Although its pathogenesis is still controversial, there is some evidence for a direct suppressive effect of T-lymphocytes on erythropoiesis [4, 5, 6, 7, 8]. Several immunosuppressive and/or immunoregulatory drugs, including CsA, have been tried with success in a number of cases [9, 10, 11].…”