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

• DOI: 10.4049/jimmunol.173.12.7324
• Publication Date: 2014-04-20T22:18:22Z
• Authors: 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; William G. Kerr
• Keywords: CD4-Positive T-Lymphocytes; Immunosuppression Therapy; Mice, Knockout; Antigen Presentation; Mice, Inbred BALB C; 0303 health sciences; Epitopes, T-Lymphocyte; Cell Differentiation; CD8-Positive T-Lymphocytes; Cytotoxicity Tests, Immunologic; Lymphocyte Activation; Coculture Techniques; Phosphoric Monoester Hydrolases; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Animals; Myeloid Cells; Lymph Nodes; Spleen; Bone Marrow Transplantation

AbstractPreviously 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.