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Acquired CD40-ligand deficiency in chronic lymphocytic leukemia

Nature Medicine volume 3, pages 984–989 (1997)Cite this article

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.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093-0663, USA

    Mark Cantwell, Tinh Hua, Jim Pappas & Thomas J. Kipps

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  4. Thomas J. Kipps
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Cantwell, M., Hua, T., Pappas, J. et al. Acquired CD40-ligand deficiency in chronic lymphocytic leukemia. Nat Med 3, 984–989 (1997). https://doi.org/10.1038/nm0997-984

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