In vitro sensitivity of post-bone marrow transplantation CFU-GM and BFU-E to TNF-α and IFN-γ Journal Article

Authors: Papadakis, V.; Ferguson, K. F.; Heller, G.; Kernan, N. A.
Article Title: In vitro sensitivity of post-bone marrow transplantation CFU-GM and BFU-E to TNF-α and IFN-γ
Abstract: Graft failure remains one of the limitations of successful marrow transplantation. T cell-depleted (TCD) bone marrow transplantation (BMT) is reported to have a higher incidence of graft failure than unmodified (UM) BMT. In most cases of secondary graft failure, no cellular immune mechanism has been identified and etiology remains unclear. In an effort to delineate a cytokine-mediated mechanism of secondary graft failure, we investigated colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) growth and pattern of inhibition by tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ) in the early post-transplant period (day 28). Gradient-separated bone marrow mononuclear cells (BMMNC) from 38 recipients of TCD BMT, 15 recipients of UM BMT, and 23 normal donors (NLD) were plated in cultures of semisolid, serum-containing medium with the addition of stem cell factor (SCF), erythropoietin (Epo), and granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Three to seven times more CFU-GM and BFU-E colonies were cultured from NLD BM-derived BMMNC than from BMMNC of recipients of TCD or UM BMT (p = 0.0001). There was no difference in colony number between recipients of UM and TCD BMT on day 28 post-transplant, however. Under G-CSF culture conditions, CFU-GM colonies from recipients of UM and TCD BMT were more susceptible (p ≤ 0.05) to suppression by IFN-γ at concentrations of 1 and 100 U/mL than NLD BMMNC-derived colonies. No other difference in IFN-γ inhibition was detected among the three groups. Under G-CSF and GM-CSF culture conditions, maximal inhibition was obtained at TNF-α concentrations > 10 ng/mL. Although early post-transplant BMMNC was more sensitive to inhibition than NLD-derived BMMNC, overall, no difference in colony growth or percent of inhibition induced by TNF-α or IFN-γ was observed between recipients of unmodified and T cell-depleted transplants. In this series, two recipients of TCD BM and one recipient of UM BMT developed graft failure; no distinct pattern of colony growth or colony inhibition was evident for those patients. The optimized in vitro conditions and specific cytokines used in this study do not indicate any quantitative or qualitative differences in the hematopoietic progenitors present in recipients of unmodified and T cell-depleted bone marrow early post-transplant to explain an increased risk of graft failure following a T cell-depleted BMT compared to an unmodified BMT.
Keywords: adolescent; adult; child; controlled study; human tissue; child, preschool; middle aged; major clinical study; interferon; t-lymphocytes; bone marrow cells; cell division; stem cell factor; erythropoietin; granulocyte macrophage colony stimulating factor; graft failure; tumor necrosis factor-alpha; gamma interferon; hematopoietic stem cell; graft rejection; macrophages; bone marrow transplantation; colony-forming units assay; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; colony forming unit gm; tumor necrosis factor; erythroid progenitor cells; granulocyte-macrophage colony-stimulating factor; bone marrow purging; hematopoietic progenitors; interferon type ii; granulocytes; burst forming unit e; humans; human; male; female; priority journal; article
Journal Title: Experimental Hematology
Volume: 23
Issue: 14
ISSN: 0301-472X
Publisher: Elsevier Science, Inc.  
Date Published: 1995-12-01
Start Page: 1422
End Page: 1430
Language: English
PUBMED: 8542927
PROVIDER: scopus
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Nancy Kernan
    485 Kernan
  2. Glenn Heller
    372 Heller