Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-54616 - Modification of T cell responses by stem cell mobilization requires direct signalling of the T cell by G-CSF and IL-10
Released on 3 February 2014, last updated on 3 June 2014
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. Single colour, Illumina MouseRef-8 v2.0 Beadarrays.
transcription profiling by array
Glen M Boyle <Glen.Boyle@qimr.edu.au>, Alistair L Don, Bruce R Blazar, Frederik Otzen Bagger, Geoffrey R Hill, Glen Boyle, Helen Morris, Kate A Markey, Katie E Lineburg, Kelli P MacDonald, Laetitia Le Texier, Lucie Leveque, Ping Zhang, Rachel D Kuns, Slavica Vuckovic