ACQUIRED CD40-LIGAND DEFICIENCY IN CHRONIC LYMPHOCYTIC-LEUKEMIA

Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an imm unodeficiency with many characteristics similar to those of persons wi th inherited defects in the gene encoding the CD40-ligand (CD154). We found that the blood and splenic CD4(+) T cells of patients with CLL f ailed to express surface CD154 after CD3 ligation. However, using an e nzyme-linked immunosorbent assay (ELISA)-based quantitative competitiv e polymerase chain reaction (PCR), we noted that CD3 ligation could in duce such T cells to express CD154 messenger RNA at levels similar to that of CD3-activated T cells from normal donors. Moreover, addition o f Increasing numbers of CLL B cells to activated normal donor T cells rapidly resulted in progressively greater down-modulation of CD154. Su ch down-modulation of CD154 could be blocked by addition of CD40 monoc lonal antibody to cultures in vitro. We propose that leukemia cell-med iated down-modulation of CD154 on activated T cells accounts for some of the acquired immune defects of patients with CLL.