| Item type: | Article | ||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Experimental hematology | ||||||||||||||||||||||||||||||||
| Publisher: | ELSEVIER SCIENCE INC | ||||||||||||||||||||||||||||||||
| Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||||||
| Volume: | 35 | ||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 1 | ||||||||||||||||||||||||||||||||
| Page Range: | pp. 155-63 | ||||||||||||||||||||||||||||||||
| Date: | 2007 | ||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Keywords: | BONE-MARROW-TRANSPLANTATION; IDIOPATHIC PNEUMONIA SYNDROME; TERM FOLLOW-UP; TOTAL-BODY IRRADIATION; TNF-ALPHA; FACTOR RECEPTORS; CONTROLLED TRIAL; LIPOPOLYSACCHARIDE STIMULATION; COMPARING METHOTREXATE; CYTOKINE DYSREGULATION; | ||||||||||||||||||||||||||||||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Yes | ||||||||||||||||||||||||||||||||
| Item ID: | 14497 |
Web of ScienceAbstract
Objective. Tumor necrosis factor alpha (TNF alpha) is an old foe in allogeneic bone marrow transplantation (allo-BMT) promoting acute graft-versus-host disease (aGVHD). We investigated to what extent donor T cells contribute to TNF alpha production. Methods. Lethally irradiated B6D2F1 mice were transplanted with bone marrow (BM) and T cells from syngeneic B6D2F1 or allogeneic B6 donors and ...
Abstract
Objective. Tumor necrosis factor alpha (TNF alpha) is an old foe in allogeneic bone marrow transplantation (allo-BMT) promoting acute graft-versus-host disease (aGVHD). We investigated to what extent donor T cells contribute to TNF alpha production. Methods. Lethally irradiated B6D2F1 mice were transplanted with bone marrow (BM) and T cells from syngeneic B6D2F1 or allogeneic B6 donors and assessed for cytokine production, aGVHD, and survival. Results. Analysis of serum TNF alpha kinetics in recipients of allogeneic B6 wild-type BM and wild-type T cells revealed that TNF alpha levels peaked around day 7 after allo-BMT, whereas TNF alpha was undetectable in syngeneic controls. TNF alpha was produced by both host and donor cells. Further exploration showed that specifically donor CD4(+) but not CD8(+) T cells were the primary donor cell source of TNF alpha at this early time point; numbers of TNF alpha expressing splenic CD4(+) T cells were higher than CD8+ T cells 7 days after allo-BMT, and maximal serum TNF alpha levels were detected following allo-BMT with only CD4(+) T cells compared to levels found in allogeneic recipients of only wild-type CD8(+) or to only CD4(+) TNF alpha(-/-) T cells. Concurrent with increased TNFa levels, early clinical aGVHD and mortality were more severe following allo-BMT with either wild-type CD4(+) and CD8(+) or CD4(+) T cells only. Conclusion. Our data demonstrate that in addition to residual host cells donor CD4(+) T cells significantly contribute to the proinflammatory cytokine milieu engendered early after alloBMT through the production of TNF alpha. These findings support strategies focusing on TNF alpha neutralization as primary treatment for aGVHD. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.
Metadata last modified: 29 Sep 2021 07:37
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