Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia
Författare
Summary, in English
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.
Publiceringsår
2014-01-16
Språk
Engelska
Sidor
7-422
Publikation/Tidskrift/Serie
Blood
Volym
123
Issue
3
Dokumenttyp
Artikel i tidskrift
Förlag
American Society of Hematology
Nyckelord
- Animals
- Bone Marrow Cells
- Disease Models, Animal
- Female
- Histocompatibility Antigens Class I
- Immunoglobulin G
- Integrin beta3
- Megakaryocytes
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, SCID
- Platelet Transfusion
- Spleen
- T-Lymphocytes
- Thrombocytopenia
- Time Factors
- Journal Article
- Research Support, Non-U.S. Gov't
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1528-0020