title: Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia.
abstract: Platelet transfusions are life-saving treatments for many patients with thrombocytopenia; however, their use is generally discouraged in the autoimmune disorder known as immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected antiplatelet CD61-induced ITP. BALB/c CD61 knockout mice (CD61(-)/H-2(d)) were immunized against platelets from wild-type syngeneic BALB/c (CD61(+)/H-2(d)), allogeneic C57BL/6 (CD61(+)/H-2(b)), or C57BL/6 CD61 KO (CD61(-)/H-2(b)) mice, and their splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP. When nondepleted splenocytes were transferred to induce antibody-mediated ITP, both CD61(+) platelet immunizations generated immunity that caused thrombocytopenia independently of allogeneic MHC molecules. In contrast, when B-cell-depleted splenocytes were transferred to induce T-cell-mediated ITP, transfer of allogeneic MHC-immunized splenocytes completely prevented CD61-induced ITP development. In addition, allogeneic platelet transfusions into SCID mice with established CD61-induced ITP rescued the thrombocytopenia. Compared with thrombocytopenic mice, bone marrow histology in the rescued mice showed normalized megakaryocyte morphology, and in vitro CD61-specific T-cell cytotoxicity was significantly suppressed. These results indicate that antibody-mediated ITP is resistant to allogeneic platelet transfusions, while the T-cell-mediated form of the disease is susceptible, suggesting that transfusion therapy may be beneficial in antibody-negative ITP.
authors.affiliation: The Toronto Platelet Immunobiology Group.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Speck
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Aslam
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.forename: Christopher G J
authors.initials: CG
authors.lastname: McKenzie
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D039661:Integrin beta3 / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D017713:Platelet Transfusion / Q000379:methods*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D013921:Thrombocytopenia / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D039661:Integrin beta3