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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Klin. Padiatr. 221, 344-350 (2009)
Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems beneficial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL/6 mice were reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6-9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The difference between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25+CD4+ regulatory T cells since their depletion did not abrogate the therapeutic effect of ICOSL blockade. Microarray analysis revealed IFN-gamma and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
bone marrow transplantation; GVHD; ICOS; T cells
ISSN (print) / ISBN
0300-8630
e-ISSN
1439-3824
Journal
Klinische Pädiatrie
Quellenangaben
Volume: 221,
Issue: 6,
Pages: 344-350
Publisher
Thieme
Publishing Place
Stuttgart
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Protection (ISS)