Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors.
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.
Takaue
Y
Y
Department of Pediatrics, University Hospital of Tokushima, Japan.
Reading
C L
CL
Watanabe
T
T
Kawano
Y
Y
Ninomiya
T
T
Iishi
Y
Y
Kosaka
M
M
Shimizu
E
E
Ichioka
T
T
Hosoda
T
T
D000741:Anemia, Aplastic / Q000473:pathology; D002455:Cell Division; D002648:Child; D003114:Colony-Forming Units Assay / Q000379:methods*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013601:T-Lymphocytes / Q000502:physiology*