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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 14, 2009 |
| Title |
Role of ICOS:ICOSL interaction in acute GVHD |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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 benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and 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 diff erence 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 eff ect of ICOSL blockade. Microarray analysis revealed IFN- γ 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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| Overall design |
B6 recipients were irradiated with 10.0 Gray, administered from a 137 Cs source. Splenocytes from C3H mice were prepared as single cell suspensions in PBS, depleted of red blood cells and counted. 2 – 3 × 10^7 C3H splenocytes in a volume of 200 μl were transplanted into B6 recipients via tail vein injection (4 mice per group per experiment) 4 – 6 h after irradiation. Mice in the treatment group with anti-ICOSL mAb and their respective controls, received 500 μg mAb i. p starting at day 0 or day 3, followed by subsequent injections of 200 μg of mAb every other day. At day 4 after transplantation RNA of spleen cells was prepared and subjected to microarray analysis. Combined RNA from allogeneic transplanted mice was hybridized onto 2 independent arrays.
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| Contributor(s) |
Mollweide A, Staege M, Burdach S, Richter G |
| Citation(s) |
19890785 |
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| Submission date |
Sep 07, 2009 |
| Last update date |
Jan 08, 2019 |
| Contact name |
Guenther HS Richter |
| E-mail(s) |
[email protected]
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| Fax |
+49-89-3068 3791
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| URL |
http://www.kind.med.tu-muenchen.de/cms/front_content.php
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| Organization name |
Klinikum rechts der Isar, TU-Muenchen
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| Department |
Pediatrics & Children's Cancer Research Center
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| Lab |
Laboratory f. Functional Genomics & Transplantation Biology
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| Street address |
Parzivalstr. 16
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| City |
Munich |
| ZIP/Postal code |
D-80804 |
| Country |
Germany |
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| Platforms (1) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
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| Samples (7)
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| GSM450397 |
syngen transplanted C57BL/6 mice |
| GSM450398 |
allogeneic transplanted, isotype treated mice, sample 1 |
| GSM450399 |
allogeneic transplanted, isotype treated mice, sample 2 |
| GSM450400 |
allogeneic transplanted, anti-ICOSL mAb day 0 treated mice, sample 1 |
| GSM450401 |
allogeneic transplanted, anti-ICOSL mAb day 0 treated mice, sample 2 |
| GSM450402 |
allogeneic transplanted, anti-ICOSL mAb day 3 treated mice, sample 1 |
| GSM450403 |
allogeneic transplanted, anti-ICOSL mAb day 3 treated mice, sample 2 |
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| Relations |
| BioProject |
PRJNA119279 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17995_RAW.tar |
60.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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