| First Author | Chow L | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 6 | Pages | 1247-53 |
| PubMed ID | 20007808 | Mgi Jnum | J:157730 |
| Mgi Id | MGI:4436824 | Doi | 10.1182/blood-2009-09-244772 |
| Citation | Chow L, et al. (2010) A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood 115(6):1247-53 |
| abstractText | 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. |
