Modification of T Cell Responses by Stem Cell Mobilization Requires Direct Signaling of the T Cell by G-CSF and IL-10

作者：MacDonald Kelli P A^*; Le Texier Laetitia; Zhang Ping; Morris Helen; Kuns Rachel D; Lineburg Katie E; Leveque Lucie; Don Alistair L; Markey Kate A; Vuckovic Slavica; Bagger Frederik O; Boyle Glen M; Blazar Bruce R; Hill Geoffrey R

来源：The Journal of Immunology, 2014, 192(7): 3180-3189.

DOI：10.4049/jimmunol.1302315

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 hematopoietic or nonhematopoietic compartments were wild-type, IL-10(-/-), G-CSFR-/-, or combinations thereof we demonstrated that the attenuation of alloreactive T cell responses after G-CSF mobilization required direct signaling 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 immuno-modulatory 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.

• 出版日期2014-4-1