title: CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia.
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(+) 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.
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada;
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and.
authors.forename: Rick
authors.initials: R
authors.lastname: Kapur
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Rukshana
authors.initials: R
authors.lastname: Aslam
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Speck
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Anne
authors.initials: A
authors.lastname: Zufferey
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Department of Medicine, Department of Laboratory Medicine and Pathobiology, and.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Department of Medicine, Department of Laboratory Medicine and Pathobiology, and.
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Department of Medicine, Department of Laboratory Medicine and Pathobiology, and Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D039661:Integrin beta3 / Q000235:genetics; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D018951:Antigens, CD20; D039661:Integrin beta3