Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Klin Padiatr, 2009/11-2009/12;221(6):344-50.
Mollweide A[1], Staege MS, Hoeschen C, Hideo Y, Burdach S, Richter GH
Affiliations
PMID: 19890785DOI: 10.1055/s-0029-1239532
Impact factor: 1.236
Abstract
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.
MeSH terms
Animals; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Bone Marrow Transplantation; Chemokines; Drug Administration Schedule; Female; Graft vs Host Disease; Inducible T-Cell Co-Stimulator Ligand; Inducible T-Cell Co-Stimulator Protein; Interferon-gamma; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Proteins; Spleen; T-Lymphocytes; Up-Regulation
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