title: Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia.
abstract: Immune thrombocytopenia (ITP) is a bleeding disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. Several reports have observed that ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP, we analyzed Tregs in the spleen and thymus. CD61 knockout mice were immunized against wild-type (CD61+) platelets, and their splenocytes were transferred into severe combined immunodeficient (SCID) mice. Compared with SCID mice receiving naive splenocytes, within 2 weeks after transfer, the ITP SCID mice became thrombocytopenic (< 200 × 10(9) platelets/L) and had increased serum anti-CD61 antibodies. The quantity of thymic Tregs by 2 weeks after transfer was significantly elevated, whereas Tregs in the spleens were significantly reduced. Treatment of the ITP mice with 2 g/kg intravenous immunoglobulin raised the platelet counts, reduced antibody production, and normalized the thymic and splenic Treg populations. Compared with thymocytes from ITP mice treated with intravenous immunoglobulin, thymocytes from untreated ITP mice delayed the onset of ITP when administered before engraftment with immune splenocytes. These results suggest that ITP in mice is associated with a peripheral Treg deficiency because of thymic retention and therapy normalizes the Tregs.
authors: Toronto Platelet Immunobiology Group, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, ON.
authors: Rukhsana
authors: R
authors: Aslam
authors: Yu
authors: Y
authors: Hu
authors: Simon
authors: S
authors: Gebremeskel
authors: George B
authors: GB
authors: Segel
authors: Edwin R
authors: ER
authors: Speck
authors: Li
authors: L
authors: Guo
authors: Michael
authors: M
authors: Kim
authors: Heyu
authors: H
authors: Ni
authors: John
authors: J
authors: Freedman
authors: John W
authors: JW
authors: Semple
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007154:Immune System Diseases; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D039661:Integrin beta3 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009928:Organ Specificity; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013921:Thrombocytopenia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000906:Antibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016756:Immunoglobulins, Intravenous; D039661:Integrin beta3; D053645:Interleukin-2 Receptor alpha Subunit