Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors

• Published in: American journal of hematology Vol. 32; no. 3; p. 205
• Main Authors: Takaue, Y, Reading, C L, Watanabe, T, Kawano, Y, Ninomiya, T, Iishi, Y, Kosaka, M, Shimizu, E, Ichioka, T, Hosoda, T
• Format: Journal Article
• Language: English
• Published: United States 01-11-1989
• Subjects: Anemia, Aplastic - pathology; Cell Division; Child; Colony-Forming Units Assay - methods; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - pathology; Humans; Infant, Newborn; Killer Cells, Natural - physiology; Male; Middle Aged; Reference Values; T-Lymphocytes - physiology
• ISSN: 0361-8609
• DOI: 10.1002/ajh.2830320309

We have used limiting-dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T-cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single-hit kinetics both before and after T-cell removal, indicating that, in the presence of colony-stimulating activity, T-cell have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T-cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T-cells were removed from this sample, the progenitor growth showed single-hit kinetics. The suppressive action of E-rosette-positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T gamma lymphocytosis. Poor progenitor-cell growth in three other patients with aplastic anemia was not significantly altered by T-cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell-mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.