In:
Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5237-5237
Abstract:
Inducible costimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. The abundant expression of ICOSL in a variety of target tissues of acute graft versus host disease (GVHD) provided the rationale to investigate its role in acute GVHD development. C57BL/6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking reagents. Mice reconstituted with allogeneic spleen cells experienced 12–16% weight loss around day 4 after transplantation and died untreated of acute GVHD within 7–10 days after transplantation. Mice treated from day 3 after transplantation with an anti-ICOSL mAb gained weight again and survived for additional 18 days, although the treatment was already stopped at day 11 after transplantation. Such mice revealed less T cells in spleen at day 4 after transplantation with reduced effector activity. 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. Similarly, depletion of NK cells did not improve prophylactic anti-ICOSL treatment. However, our results clearly show that delayed, i.e. therapeutic blockade of ICOS:ICOSL interaction can interfere with acute GVHD development and alleviates disease significantly in a polyclonal T cell setting.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V106.11.5237.5237
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2005
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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