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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
; ; ; ; ; ; ; ; and
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
  • pmid:26556550
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
2022-05-22 00:35:53
@article{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}},
  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}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{6}},
  pages        = {{8--735}},
  publisher    = {{American Society of Hematology}},
  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}},
  doi          = {{10.1182/blood-2015-06-655126}},
  volume       = {{127}},
  year         = {{2016}},
}