Acquired CD40-ligand deficiency in chronic lymphocytic leukemia.
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.
Cantwell
M
M
Department of Medicine, UCSD School of Medicine, La Jolla, California 92093-0663, USA.
Hua
T
T
Pappas
J
J
Kipps
T J
TJ
D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012995:Solubility
D017252:CD3 Complex; D019013:CD40 Antigens; D017931:DNA Primers; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D023201:CD40 Ligand