CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia
Författare
Summary, in English
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.
Publiceringsår
2016-02-11
Språk
Engelska
Sidor
8-735
Publikation/Tidskrift/Serie
Blood
Volym
127
Issue
6
Dokumenttyp
Artikel i tidskrift
Förlag
American Society of Hematology
Nyckelord
- 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
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1528-0020