Only Therapeutic ICOS:ICOSL Blockade Alleviates Acute Graft versus Host Disease
| Autor: | Martin S. Staege, Gunther Richter, Christoph Hoeschen, S. Burdach, A. Mollweide, Y. Hideo |
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| Rok vydání: | 2009 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Chemokine T-Lymphocytes T cell Graft vs Host Disease Spleen Drug Administration Schedule Inducible T-Cell Co-Stimulator Protein Inducible T-Cell Co-Stimulator Ligand Interferon-gamma Mice Animals Medicine IL-2 receptor Bone Marrow Transplantation Oligonucleotide Array Sequence Analysis Mice Inbred C3H biology business.industry Therapeutic effect Antibodies Monoclonal Proteins medicine.disease Up-Regulation Blockade Mice Inbred C57BL Transplantation surgical procedures operative medicine.anatomical_structure Graft-versus-host disease Pediatrics Perinatology and Child Health Immunology biology.protein Female Chemokines business |
| Zdroj: | Klinische Pädiatrie. 221:344-350 |
| ISSN: | 1439-3824 0300-8630 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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