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Publication : Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses.

First Author  Ghansah T Year  2004
Journal  J Immunol Volume  173
Issue  12 Pages  7324-30
PubMed ID  15585856 Mgi Jnum  J:94861
Mgi Id  MGI:3521619 Doi  10.4049/jimmunol.173.12.7324
Citation  Ghansah T, et al. (2004) Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses. J Immunol 173(12):7324-30
abstractText  Previously we demonstrated that SHIP(-/-) mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study we show that SHIP(-/-) splenocytes and lymph node cells are poor stimulators of allogeneic T cell responses that cause GvHD. Intriguingly, SHIP(-/-) splenocytes prime naive T cell responses to peptide epitopes, but, conversely, are partially impaired for priming T cell responses to whole Ag. However, dendritic cells (DC) purified from SHIP(-/-) splenocytes prime T cell responses to allogeneic targets, peptide epitopes, and whole Ag as effectively as SHIP(+/+) DC. These findings point to an extrinsic effect on SHIP(-/-) DC that impairs priming of allogeneic T cell responses. Consistent with this extrinsic effect, we found that a dramatic expansion of myeloid suppressor cells in SHIP(-/-) mice impairs priming of allogeneic T cells. These findings suggest that SHIP expression or its activity could be targeted to selectively compromise T cell responses that mediate GvHD and graft rejection.
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