Effects of CD70 and CD11a in immune thrombocytopenia patients

J Clin Immunol. 2011 Aug;31(4):632-42. doi: 10.1007/s10875-011-9539-1. Epub 2011 May 4.

Abstract

Introduction: CD70 and CD11a are co-stimulatory molecules that are important for the immune functions of T, B lymphocytes. Over-expressions of CD70 or CD11a cause T cell to be autoreactive.

Objectives: The purpose of this study was to explore the effect of CD70 and CD11a in immune thrombocytopenia (ITP).

Methods: CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were measured respectively by real-time quantitative-PCR (RT-PCR) and flow cytometry. The apoptosis of T cells, B cells, and platelets in the PBMCs were analyzed by flow cytometry, and secretion of IL-4, IFN-γ, as well as IgG in the reaction supernatant were detected by ELISA. In order to investigate the effects of CD70 and CD11a over-expression on pathogenesis of ITP, anti-CD70, and anti-CD11a mAbs were used to block the signaling pathways.

Results: CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were significantly higher than healthy controls. In vitro co-culturing of PBMCs with anti-CD70 or anti-CD11a, the apoptosis of T, B lymphocytes were significantly increased but apoptosis of platelets were reduced. Anti-CD11a and anti-CD70 both significantly suppressed the secretion of IFN-γ, while anti-CD11a significantly promoted the secretion of IL-4. There was no significant difference in the healthy group.

Conclusions: CD70 and CD11a facilitate the survival of T, B lymphocytes and indirectly enhance the destruction of platelets in ITP. Blockade of CD70 or CD11a are promising therapeutic approaches for ITP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Apoptosis / immunology
  • Autoimmune Diseases / therapy
  • B-Lymphocytes / metabolism
  • Blood Platelets / metabolism
  • CD11a Antigen / blood*
  • CD11a Antigen / immunology*
  • CD27 Ligand / blood*
  • CD27 Ligand / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / blood
  • Real-Time Polymerase Chain Reaction
  • Thrombocytopenia / immunology*
  • Thrombocytopenia / metabolism
  • Thrombocytopenia / therapy

Substances

  • Antibodies, Monoclonal
  • CD11a Antigen
  • CD27 Ligand
  • Immunoglobulin G
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma