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Expansion of Myeloid Suppressor Cells in SHIP-Deficient Mice Represses Allogeneic T Cell Responses

2004; American Association of Immunologists; Volume: 173; Issue: 12 Linguagem: Inglês

10.4049/jimmunol.173.12.7324

1550-6606

Tomar Ghansah, Kim H.T. Paraiso, Steven L. Highfill, Caroline Desponts, Sarah May, Joseph K. McIntosh, Wang Jiawang, John M. Ninos, Jason Brayer, Fengdong Cheng, Eduardo M. Sotomayor, William G. Kerr,

T-cell and B-cell Immunology

Abstract 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.