CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia
(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
- 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
- publishing date
- 2016-02-11
- 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
- 2024-07-26 18:46:56
@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}}, }