Related Experiment Video
Updated: May 5, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
Acquired CD40-ligand deficiency in chronic lymphocytic leukemia
1Department of Medicine, UCSD School of Medicine, La Jolla, California 92093-0663, USA.
Insights
Chronic lymphocytic leukemia (CLL) patients exhibit immune deficiencies due to impaired CD40-ligand (CD154) expression on T cells. Leukemia cells down-modulate CD154, contributing to these acquired immune defects.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- Patients with B-cell chronic lymphocytic leukemia (CLL) often develop acquired immunodeficiencies.
- These immune defects share similarities with inherited deficiencies in the CD40-ligand (CD154) gene.
Purpose of the Study:
- To investigate the mechanism of CD154 expression defects in T cells from CLL patients.
- To determine the role of CLL B cells in the down-modulation of CD154 on T cells.
Main Methods:
- Analysis of surface CD154 expression on T cells after CD3 ligation.
- Quantitative competitive polymerase chain reaction (PCR) to measure CD154 messenger RNA (mRNA) levels.
- In vitro co-culture experiments with CLL B cells and activated normal T cells, with and without CD40 monoclonal antibody.
Main Results:
- CD4+ T cells from CLL patients failed to express surface CD154 upon CD3 ligation.
- CD154 mRNA was induced in CLL T cells to levels comparable to normal T cells after CD3 activation.
- CLL B cells progressively down-modulated CD154 expression on activated normal T cells.
- Addition of CD40 monoclonal antibody blocked this down-modulation.
Conclusions:
- Leukemia cell-mediated down-modulation of CD154 on activated T cells is a significant factor in the acquired immune defects observed in CLL patients.
- Understanding this mechanism may lead to novel therapeutic strategies for managing immune dysfunction in CLL.
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.
