A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell–mediated responses that are differentially sensitive to therapy

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody-opsonized platelets being prematurely destroyed in the spleen, although some patients with ITP may have a cell-mediated form of thrombocytopenia. Although several animal models of ITP have been developed, few mimic primar...

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Bibliographic Details
Published in:	Blood Vol. 115; no. 6; pp. 1247 - 1253
Main Authors:	Chow, Leola, Aslam, Rukhsana, Speck, Edwin R., Kim, Michael, Cridland, Norman, Webster, Michelle Lee, Chen, Pingguo, Sahib, Kim, Ni, Heyu, Lazarus, Alan H., Garvey, M. Bernadette, Freedman, John, Semple, John W.
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 11-02-2010 Americain Society of Hematology
Subjects:	Animals Antigens, CD19 - immunology Biological and medical sciences Blood Platelets - immunology CD8-Positive T-Lymphocytes - immunology Disease Models, Animal Female Flow Cytometry Hematologic and hematopoietic diseases Immunoglobulins, Intravenous - administration & dosage Integrin beta3 - immunology Lymphocyte Depletion Medical sciences Megakaryocytes - physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, SCID Platelet Count Platelet diseases and coagulopathies Purpura, Thrombocytopenic, Idiopathic - immunology Purpura, Thrombocytopenic, Idiopathic - pathology Purpura, Thrombocytopenic, Idiopathic - therapy Spleen - physiology T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - pathology Thrombocytopenia Animal model Immune response Hematology Antibody Rodentia Hemopathy Vertebrata Platelet Mammalia Treatment Mouse CD8 T lymphocyte
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Summary:	Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody-opsonized platelets being prematurely destroyed in the spleen, although some patients with ITP may have a cell-mediated form of thrombocytopenia. Although several animal models of ITP have been developed, few mimic primary chronic ITP nor have any shown cell-mediated platelet destruction. To create this type of model, splenocytes from CD61 knockout mice immunized against CD61+ platelets were transferred into severe combined immunodeficient (SCID) (CD61+) mouse recipients, and their platelet counts and phenotypes were observed. As few as 5 × 104 splenocytes induced a significant thrombocytopenia and bleeding mortality (80%) in recipients within 3 weeks after transfer. Depletion of lymphocyte subsets before transfer showed that the splenocyte's ability to induce thrombocytopenia and bleeding completely depended on CD4+ T helper cells and that both CD19+ B cell (antibody)– and CD8+ T cell (cell)–mediated effector mechanisms were responsible. Treatment of the SCID mouse recipients with intravenous γ-globulins raised platelet counts and completely prevented bleeding mortality induced by antibody-mediated effector mechanisms but did not affect cell-mediated disease. This novel model not only shows both antibody- and cell-mediated ITP and bleeding but also suggests that these 2 effector mechanisms have a differential response to therapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood-2009-09-244772