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

Abstract

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 x 10(4) 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 gamma-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.

• Authors: Leola Chow, Rukhsana Aslam, Edwin R Speck, Michael Kim, Norman Cridland, Michelle Lee Webster, Pingguo Chen, Kim Sahib, Heyu Ni, Alan H Lazarus, M Bernadette Garvey, John Freedman, John W Semple
• Journal: Blood (Blood) Vol. 115 Issue 6 Pg. 1247-53 (Feb 11 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 20007808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD19
• Immunoglobulins, Intravenous
• Integrin beta3

Topics

• Animals
• Antigens, CD19 (immunology)
• Blood Platelets (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Female
• Flow Cytometry
• Immunoglobulins, Intravenous (administration & dosage)
• Integrin beta3 (immunology)
• Lymphocyte Depletion
• Megakaryocytes (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, SCID
• Platelet Count
• Purpura, Thrombocytopenic, Idiopathic (immunology, pathology, therapy)
• Spleen (physiology)
• T-Lymphocytes, Helper-Inducer (immunology, pathology)