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CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia

Guo, Li LU ; Kapur, Rick; Aslam, Rukshana; Speck, Edwin R; Zufferey, Anne; Zhao, Yajing; Kim, Michael; Lazarus, Alan H; Ni, Heyu and Semple, John W LU (2016) In Blood 127(6). p.8-735
Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8(+) T-cell-mediated ITP using a murine model. CD61 knockout (KO) mice were immunized with CD61(+) platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD61(+)... (More)

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8(+) T-cell-mediated ITP using a murine model. CD61 knockout (KO) mice were immunized with CD61(+) platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD61(+) platelet immunization. This resulted in efficient Bdep in vivo, accompanied by significant increases in splenic and lymph node CD4(+) and CD8(+) T cells and proportional increases of FOXP3(+) in CD4(+)and CD8(+) T cells. Moreover, Bdep therapy resulted in significantly decreased splenic CD8(+) T-cell proliferation in vitro that could be rescued by interleukin-2. This correlated with normalization of in vivo platelet counts in the transferred SCID mice suggesting that anti-CD20 therapy significantly reduces the ability of CD8(+) T cells to activate and mediate ITP.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antigens, CD20, B-Lymphocytes, CD8-Positive T-Lymphocytes, Integrin beta3, Lymphocyte Depletion, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Platelet Count, Purpura, Thrombocytopenic, Idiopathic, Journal Article, Research Support, Non-U.S. Gov't
in
Blood
volume
127
issue
6
pages
4 pages
publisher
American Society of Hematology
external identifiers
  • Scopus:84959323543
ISSN
1528-0020
DOI
10.1182/blood-2015-06-655126
language
English
LU publication?
no
id
d709c0ec-7943-48da-91f9-b363369903c4
date added to LUP
2016-09-23 11:56:40
date last changed
2016-10-13 05:14:11
@misc{d709c0ec-7943-48da-91f9-b363369903c4,
  abstract     = {<p>Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8(+) T-cell-mediated ITP using a murine model. CD61 knockout (KO) mice were immunized with CD61(+) platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD61(+) platelet immunization. This resulted in efficient Bdep in vivo, accompanied by significant increases in splenic and lymph node CD4(+) and CD8(+) T cells and proportional increases of FOXP3(+) in CD4(+)and CD8(+) T cells. Moreover, Bdep therapy resulted in significantly decreased splenic CD8(+) T-cell proliferation in vitro that could be rescued by interleukin-2. This correlated with normalization of in vivo platelet counts in the transferred SCID mice suggesting that anti-CD20 therapy significantly reduces the ability of CD8(+) T cells to activate and mediate ITP.</p>},
  author       = {Guo, Li and Kapur, Rick and Aslam, Rukshana and Speck, Edwin R and Zufferey, Anne and Zhao, Yajing and Kim, Michael and Lazarus, Alan H and Ni, Heyu and Semple, John W},
  issn         = {1528-0020},
  keyword      = {Animals,Antigens, CD20,B-Lymphocytes,CD8-Positive T-Lymphocytes,Integrin beta3,Lymphocyte Depletion,Mice,Mice, Inbred BALB C,Mice, Inbred C57BL,Mice, Knockout,Mice, SCID,Platelet Count,Purpura, Thrombocytopenic, Idiopathic,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {02},
  number       = {6},
  pages        = {8--735},
  publisher    = {ARRAY(0xa6aaa20)},
  series       = {Blood},
  title        = {CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia},
  url          = {http://dx.doi.org/10.1182/blood-2015-06-655126},
  volume       = {127},
  year         = {2016},
}