Rh autoantigen presentation to helper T cells in chronic lymphocytic leukemia by malignant B cells

Andrew Michael Hall, Mark Adrian Vickers, Ewen McLeod, Robert Norman Barker

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune diseases directed against constituents of the blood, including hemolytic anemia (AIHA). We hypothesized that CLL cells predispose to hematologic autoimmunity by acting as aberrant antigen-presenting cells (APCs). Initially, it was confirmed that all studied patients with AIHA secondary to CLL harbored activated helper T (T(H)) cells specific for epitopes on the dominant red blood cell (RBC) autoantigens in primary AIHA, the Rh proteins. Rh-specific T(H) cells were also detected in a number of patients with CLL who, although they did not have AIHA, had low levels of anti-RBC antibody in their sera. Fractionation of putative APC populations from the peripheral blood of patients by negative selection showed that CD5+ CLL cells are the most effective cell type in processing and presenting purified Rh protein to autoreactive T(H) cells. This ability was confirmed using positively selected CD5+ CLL cells. Thus, our study provides the first evidence for malignant cells driving an autoimmune response by acting as aberrant APCs.
Original languageEnglish
Pages (from-to)2007-2015
Number of pages9
JournalBlood
Volume105
Issue number5
Early online date29 Jul 2004
DOIs
Publication statusPublished - 1 Mar 2005

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Specificity
  • Antigen Presentation
  • Antigens, CD5
  • Autoantibodies
  • Autoantigens
  • Autoimmune Diseases
  • B-Lymphocytes
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Male
  • Middle Aged
  • Rh-Hr Blood-Group System
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes, Helper-Inducer

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