Granulocyte colony-stimulating factor (CSF) but not interleukin-1 (IL-1), IL-3, and granulocyte-macrophage CSF protect bone marrow progenitor cells from suppression by allosensitized cytotoxic T cells Journal Article


Authors: Gerritsen, W. R.; O'Reilly, R. J.
Article Title: Granulocyte colony-stimulating factor (CSF) but not interleukin-1 (IL-1), IL-3, and granulocyte-macrophage CSF protect bone marrow progenitor cells from suppression by allosensitized cytotoxic T cells
Abstract: The major immunological reactions after an allogeneic bone marrow transplantation (BMT) are graft rejection and graft-versus-host disease (GVHD). GVHD can be prevented by T-cell depletion of the allogeneic BM graft, but the beneficial effect of T-cell depletion on the incidence of GVHD is counterbalanced by a higher incidence of graft failure. One option for the prevention of graft rejection after T-cell-depleted BM grafts is the administration of cytokines. Before applying cytokines after an allogeneic BMT, we considered it desirable to learn whether cytokines would alter the susceptibility of donor BM cells to host T cells. An in vitro assay was developed to investigate the role of the cytokines interleukin-1 (IL-1), IL- 3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) on the interaction between allosensitized, cytotoxic-T cells (CTLs) and T-cell-depleted BM cells. CTLs primed against the BM donor suppressed the formation of colonies consisting of granulocytes and macrophages (colony-forming unit GM). Colony formation was not inhibited by CTLs sensitized against a third party. Accordingly, the number of colonies scored in cocultures with CTLs sensitized to third party antigens were designated as 0% inhibition. A 66% inhibition of colony formation was observed for untreated BM cells at an effector:target (E:T) ratio of 1:1. Pretreatment of the BM cells with the cytokines G-CSF, GM-CSF, IL-1, and IL- 3 resulted in a 38% (P = .001), 53%, 66%, and 68% inhibition of colony formation, respectively, at E:T ratios of 1:1. G-CSF reduced the susceptibility of BM cells over a range from 4:1 to 1:16 (E:T ratios). GM- CSF had only significant influence at the lower E:T ratios (1:4 and 1:16). These in vitro data indicate that G-CSF could protect BM cells from killing by allosensitized CTLs and suggest that administration of these cytokines might potentially reduce the susceptibility of T-cell-depleted allogeneic BM grafts to host T-cell-mediated rejection.
Keywords: human cell; bone marrow cells; granulocyte macrophage colony stimulating factor; allogenic bone marrow transplantation; stem cell; fluorescent antibody technique; graft failure; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; graft versus host reaction; hematopoietic stem cells; bone marrow cell; graft rejection; macrophages; colony-forming units assay; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; isoantigens; interleukin 1; interleukin-1; colony forming unit; granulocyte-macrophage colony-stimulating factor; interleukin 3; interleukin-3; granulocytes; human; priority journal; article; support, non-u.s. gov't
Journal Title: Blood
Volume: 84
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1994-09-15
Start Page: 1906
End Page: 1912
Language: English
PROVIDER: scopus
PUBMED: 7521693
DOI: 10.1182/blood.V84.6.1906.1906
DOI/URL:
Notes: Export Date: 14 January 2019 -- Article -- Source: Scopus
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  1. Richard O'Reilly
    748 O'Reilly