Allogeneic platelet transfusions prevent murine T-cell–mediated immune thrombocytopenia

Abstract

Key Points• Allogeneic platelet MHC class I transfusions can both prevent and/or alleviate anti-CD61 (GPIIIa) T-cell-mediated ITP.• The transfusions reverse abnormal bone marrow megakaryocyte histology and inhibit CD61-induced cytotoxicity.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 (CD61were immunized against platelets from wild-type syngeneic BALB/c (CD61) 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 1 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. (Blood. 2014;123(3):422-427)

CD8+ T cells are predominantly protective and required for effective steroid therapy in murine models of immune thrombocytopenia

“…). In active EIT, as previously reported, 20,59 we found transfusion of immunized b3 2/2 splenocytes into WT mice resulted in increased populations of CTLs ( Figure 4B, day 6), as well as increased CD8…”

“…BLOOD [17][18][19][20]59 As was previously reported, depletion of CD19 1 B cells before splenocyte engraftment still led to thrombocytopenia, 20 suggesting that in the absence of antibodies, CTLs alone can cause ITP and CD8…”

Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

“…[2][3][4][5]13,16 In this study, the normal range of CTL-induced platelet apoptosis was established from the mean 6 2 standard deviations of results in healthy controls. The patients with CTL-induced platelet apoptosis higher than the upper limit of normal range were assigned to the cytotoxic group (23 patients); otherwise, they were assigned to the noncytotoxic group (15 patients) ( Figure 1).…”

“…1 Cytotoxic T-lymphocyte (CTL)-mediated platelet destruction [2][3][4][5] and disturbed cytokine profiles 6,7 play important roles in the pathogenesis of ITP. Interleukin-27 (IL-27), a cytokine with both pro-inflammatory and anti-inflammatory effects, plays pleiotropic roles in immunomodulation.…”

Platelet-Derived Ectosomes Reduce NK Cell Function

“…PLT express HLA class I molecules (8,9). Many investigators showed, in animal models, that PLT transfusions were accompanied by immunosuppressive side effects probably related to MHC class I (10,11). In humans, PLT transfusion per se was accompanied by an increased susceptibility for infections, as well as tumor growth; high PLT numbers were shown to be associated with worse outcomes in patients with ovarian or other cancers (12)(13)(14)(15).…”