Acquired CD40-ligand Deficiency in Chronic Lymphocytic Leukemia

Nat Med. 1997 Sep;3(9):984-9. doi: 10.1038/nm0997-984.

Abstract

Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an immunodeficiency with many characteristics similar to those of persons with inherited defects in the gene encoding the CD40-ligand (CD154). We found that the blood and splenic CD4+ T cells of patients with CLL failed to express surface CD154 after CD3 ligation. However, using an enzyme-linked immunosorbent assay (ELISA)-based quantitative competitive polymerase chain reaction (PCR), we noted that CD3 ligation could induce such T cells to express CD154 messenger RNA at levels similar to that of CD3-activated T cells from normal donors. Moreover, addition of increasing numbers of CLL B cells to activated normal donor T cells rapidly resulted in progressively greater down-modulation of CD154. Such down-modulation of CD154 could be blocked by addition of CD40 monoclonal antibody to cultures in vitro. We propose that leukemia cell-mediated down-modulation of CD154 on activated T cells accounts for some of the acquired immune defects of patients with CLL.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Antigens / metabolism
  • CD40 Ligand
  • DNA Primers / genetics
  • Down-Regulation
  • Humans
  • In Vitro Techniques
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Ligands
  • Lymphocyte Activation
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Solubility

Substances

  • CD3 Complex
  • CD40 Antigens
  • DNA Primers
  • Ligands
  • Membrane Glycoproteins
  • RNA, Messenger
  • RNA, Neoplasm
  • CD40 Ligand