Bmi-1 regulates autoreactive CD4+ T cell survival in immune thrombocytopenia patients

J Clin Immunol. 2012 Jun;32(3):505-13. doi: 10.1007/s10875-011-9643-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Blood Platelets / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology*
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*

Substances

  • BMI1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Interleukin-4
  • Interferon-gamma
  • Polycomb Repressive Complex 1