Advanced

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

Guo, Li LU ; Yang, Lei; Speck, Edwin R; Aslam, Rukhsana; Kim, Michael; McKenzie, Christopher G J; Lazarus, Alan H; Ni, Heyu; Hou, Ming and Freedman, John, et al. (2014) In Blood 123(3). p.7-422
Abstract

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 (CD61(-)/H-2(d)) were immunized against platelets from wild-type syngeneic BALB/c (CD61(+)/H-2(d)), allogeneic C57BL/6 (CD61(+)/H-2(b)), or C57BL/6 CD61 KO (CD61(-)/H-2(b)) 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(+)... (More)

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 (CD61(-)/H-2(d)) were immunized against platelets from wild-type syngeneic BALB/c (CD61(+)/H-2(d)), allogeneic C57BL/6 (CD61(+)/H-2(b)), or C57BL/6 CD61 KO (CD61(-)/H-2(b)) 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(+) 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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Bone Marrow Cells, Disease Models, Animal, Female, Histocompatibility Antigens Class I, Immunoglobulin G, Integrin beta3, Megakaryocytes, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Platelet Transfusion, Spleen, T-Lymphocytes, Thrombocytopenia, Time Factors, Journal Article, Research Support, Non-U.S. Gov't
in
Blood
volume
123
issue
3
pages
6 pages
publisher
American Society of Hematology
external identifiers
  • scopus:84897019921
ISSN
1528-0020
DOI
10.1182/blood-2013-08-523308
language
English
LU publication?
no
id
9542947b-d5aa-4dc7-bf82-2953e5329773
date added to LUP
2016-09-23 12:01:23
date last changed
2017-05-21 04:53:58
@article{9542947b-d5aa-4dc7-bf82-2953e5329773,
  abstract     = {<p>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 (CD61(-)/H-2(d)) were immunized against platelets from wild-type syngeneic BALB/c (CD61(+)/H-2(d)), allogeneic C57BL/6 (CD61(+)/H-2(b)), or C57BL/6 CD61 KO (CD61(-)/H-2(b)) 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(+) 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.</p>},
  author       = {Guo, Li and Yang, Lei and Speck, Edwin R and Aslam, Rukhsana and Kim, Michael and McKenzie, Christopher G J and Lazarus, Alan H and Ni, Heyu and Hou, Ming and Freedman, John and Semple, John W},
  issn         = {1528-0020},
  keyword      = {Animals,Bone Marrow Cells,Disease Models, Animal,Female,Histocompatibility Antigens Class I,Immunoglobulin G,Integrin beta3,Megakaryocytes,Mice,Mice, Inbred BALB C,Mice, Inbred C57BL,Mice, Knockout,Mice, SCID,Platelet Transfusion,Spleen,T-Lymphocytes,Thrombocytopenia,Time Factors,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {7--422},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia},
  url          = {http://dx.doi.org/10.1182/blood-2013-08-523308},
  volume       = {123},
  year         = {2014},
}