title: Bmi-1 regulates autoreactive CD4+ T cell survival in immune thrombocytopenia patients.
abstract: Autoreactive T cells in immune thrombocytopenia(ITP) patients undergo a rapid clonal expansion and are resistant to apoptosis to maintain continuous effect in thrombocytopenia. As Bmi-1 is involved in memory CD4+ T cell survival and Th2 proliferation, we hypothesized that Bmi-1 may have a role in autoreactive CD4+ T cell clonal expansion and Th1/Th2 development in ITP patients. We found that CD4+ T cells from active ITP patients had a higher Bmi-1 expression in comparison with remission and healthy controls, and autoreactive CD4+ T cells had more capability to proliferate and resistance to apoptosis than that of healthy controls. We evaluated the part that Bmi-1 played in proliferation and Th1 bias condition of autoreactive CD4+ T cells in ITP. We used lentiviral transfer vectors containing Bmi-1 and shBmi-1 to infect CD4+ T cells from ITP patients and healthy controls during autologous platelets stimulation. Flow cytometry and ELISA were applied to detect various parameters. The results showed that suppression of Bmi-1 using short hairpin RNA inhibited the platelet-mediated proliferation and increased apoptosis of autoreactive CD4+ T cells from ITP patients.Increased Bmi-1 expression in CD4+ T cells from healthy controls promoted the proliferation and inhibited apoptosis of CD4+ T cells. Bmi-1 significantly promoted interleukin-4 secretion by CD4+ T cells. These findings suggest that Bmi-1 plays a part in autoreactive CD4+ T cell proliferative capability and apoptotic resistance in ITP patients.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, People’s Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Zeping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.forename: Renchi
authors.initials: R
authors.lastname: Yang
mesh_terms: D000328:Adult; D017209:Apoptosis; D001792:Blood Platelets / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D063150:Polycomb Repressive Complex 1