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Series GSE54616 Query DataSets for GSE54616
Status Public on Feb 03, 2014
Title Modification of T cell responses by stem cell mobilization requires direct signalling of the T cell by G-CSF and IL-10
Organism Mus musculus
Experiment type Expression profiling by array
Summary The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects on a broad range of cells and IL-10 is a key regulator of many of these effects. Using mixed radiation chimeras in which the haematopoietic or non-haematopoietic compartments were wild-type (WT), IL-10–/–, G-CSFR–/– or combinations thereof we demonstrated that the attenuation of alloreactive T cell responses after with G-CSF mobilization required direct signalling of the T cell by both G-CSF and IL-10. IL-10 was generated principally by radio-resistant tissue, and was not required to be produced by T cells. G-CSF mobilization significantly modulated the transcription profile of CD4+CD25+ regulatory T cells, promoted their expansion in the donor and recipient and their depletion significantly increased graft-versus-host disease (GVHD). In contrast, stem cell mobilization with the CXCR4 antagonist AMD3100 did not alter the donor T cell’s ability to induce acute GVHD. These studies provide an explanation for the effects of G-CSF on T cell function and demonstrate that IL-10 is required to license regulatory function but T cell production of IL-10 is not itself required for the attenuation GVHD. Although administration of CXCR4 antagonists is an efficient means of stem cell mobilization, this fails to evoke the immunomodulatory effects seen during G-CSF mobilization. These data provide a compelling rationale for considering the immunological benefits of G-CSF in selecting mobilization protocols for allogeneic stem cell transplantation.
Overall design Single colour, Illumina MouseRef-8 v2.0 Beadarrays.
Contributor(s) MacDonald KP, Le Texier L, Zhang P, Morris H, Kuns RD, Lineburg KE, Leveque L, Don AL, Markey KA, Vuckovic S, Otzen Bagger F, Boyle G, Blazar BR, Hill GR
Citation(s) 24585878
Submission date Feb 02, 2014
Last update date Jun 14, 2018
Contact name Glen M Boyle
Phone +61 7 3362 0319
Organization name QIMR Berghofer Medical Research Insitute
Department Department of Cell and Molecular Biology, Cancer Program
Lab Cancer Drug Mechanisms Group
Street address 300 Herston Road Herston
City Brisbane
State/province Queensland
ZIP/Postal code 4006
Country Australia
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (8)
GSM1319950 G-CSF Rep 1
GSM1319951 G-CSF Rep 2
GSM1319952 G-CSF Rep 3
BioProject PRJNA237186

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE54616_RAW.tar 3.1 Mb (http)(custom) TAR
GSE54616_non-normalized.txt.gz 932.1 Kb (ftp)(http) TXT
Processed data included within Sample table
Raw data are available on Series record

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