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Expansion of Myeloid Suppressor Cells in SHIP-Deficient Mice Represses Allogeneic T Cell Responses¹

Tomar Ghansah^*,, Kim H. T. Paraiso^*,, Steven Highfill^*,, Caroline Desponts^*,, Sarah May^*,, Joseph K. McIntosh^*,, Jia-Wang Wang^*,, John Ninos^*,, Jason Brayer^*,, Fengdong Cheng^*,, Eduardo Sotomayor^*, and William G. Kerr^2,*,,

^* Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, and Departments of Interdisciplinary Oncology and Biochemistry, University of South Florida, Tampa, FL 33612

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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