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 antibodyopsonized 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 immunizedagainstCD61plateletsweretransferred into severe combined immunodeficient (SCID) (CD61) mouse recipients, and their platelet counts and phenotypes were observed. As few as 5 104 splenocytes inducedasignificantthrombocytopeniaand bleeding mortality (80%) in recipients within 3 weeks after transfer. Depletion of lymphocyte subsets before transfer showed that thesplenocyte’sabilitytoinducethrombocytopenia and bleeding completely depended on CD4 T helper cells and that both CD19 B cell (antibody)‐ and CD8 T cell (cell)‐ mediatedeffectormechanismswereresponsible. Treatment of the SCID mouse recipients with intravenous -globulins raised platelet counts and completely prevented bleeding mortality induced by antibodymediated effector mechanisms but did not affect cell-mediated disease. This novel model not only shows both antibody- and cell-mediatedITPandbleedingbutalsosuggeststhatthese2effectormechanismshave a differential response to therapy. (Blood. 2010;115:1247-1253)