title: Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses.
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.
authors.affiliation: Immunology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, and Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Tomar
authors.initials: T
authors.lastname: Ghansah
authors.forename: Kim H T
authors.initials: KH
authors.lastname: Paraiso
authors.forename: Steven
authors.initials: S
authors.lastname: Highfill
authors.forename: Caroline
authors.initials: C
authors.lastname: Desponts
authors.forename: Sarah
authors.initials: S
authors.lastname: May
authors.forename: Joseph K
authors.initials: JK
authors.lastname: McIntosh
authors.forename: Jia-Wang
authors.initials: JW
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Ninos
authors.forename: Jason
authors.initials: J
authors.lastname: Brayer
authors.forename: Fengdong
authors.initials: F
authors.lastname: Cheng
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sotomayor
authors.forename: William G
authors.initials: WG
authors.lastname: Kerr
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases