A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy
(2010) In Blood 115(6). p.53-1247- 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... (More)
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.
(Less)
- author
- publishing date
- 2010-02-11
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Antigens, CD19, Blood Platelets, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Flow Cytometry, Immunoglobulins, Intravenous, Integrin beta3, Lymphocyte Depletion, Megakaryocytes, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Platelet Count, Purpura, Thrombocytopenic, Idiopathic, Spleen, T-Lymphocytes, Helper-Inducer, Journal Article, Research Support, Non-U.S. Gov't
- in
- Blood
- volume
- 115
- issue
- 6
- pages
- 7 pages
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:20007808
- scopus:77949536683
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2009-09-244772
- language
- English
- LU publication?
- no
- id
- 547c6648-1392-46c5-bf8f-f35af195cd99
- date added to LUP
- 2016-09-23 12:07:32
- date last changed
- 2024-11-17 07:18:33
@article{547c6648-1392-46c5-bf8f-f35af195cd99,
abstract = {{<p>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.</p>}},
author = {{Chow, Leola and Aslam, Rukhsana and Speck, Edwin R and Kim, Michael and Cridland, Norman and Webster, Michelle Lee and Chen, Pingguo and Sahib, Kim and Ni, Heyu and Lazarus, Alan H and Garvey, M Bernadette and Freedman, John and Semple, John W}},
issn = {{1528-0020}},
keywords = {{Animals; Antigens, CD19; Blood Platelets; CD8-Positive T-Lymphocytes; Disease Models, Animal; Female; Flow Cytometry; Immunoglobulins, Intravenous; Integrin beta3; Lymphocyte Depletion; Megakaryocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Spleen; T-Lymphocytes, Helper-Inducer; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
month = {{02}},
number = {{6}},
pages = {{53--1247}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy}},
url = {{http://dx.doi.org/10.1182/blood-2009-09-244772}},
doi = {{10.1182/blood-2009-09-244772}},
volume = {{115}},
year = {{2010}},
}