Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodgkin disease - Potential therapeutic significance

BACKGROUND. The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express CD30 and CD40 receptors that can activate nuclear factor kappa B and transduce survival signals, The authors have reported previously that the B lymphocytes of HID express CD30 ligand (CD30L, CD153). Furthermore, they and others have reported previously that the CD40L survival pathway is augmented in patients with B-cell malignancies, as CD40L was constitutively expressed by the malignant B cells and infiltrating T cells, and sera from those patients contained elevated levels of soluble CD40L. In this study, the authors investigated the hypothesis that the survival of H/RS cells was similarly promoted by an augmented CD40L signals in HD patients. METHODS. The expression of CD40L on lymphocyte subsets of patients with classic HD was determined by two-color fluorescent-activated cell sorter analysis. Serum soluble CD40L levels were determined by enzyme linked immunosorbent assay. RESULTS. CD40L was constitutively expressed on both the T and B cells of HD patients but was more prominently expressed on the B lymphocytes, Soluble CD40L was detected in the serum of 17 of 37 patients (45%) and was higher than 1 ng/mL in 4 patients (10%). Both interleukin (IL)-4 and IL-10, which are known to be secreted by H/RS cells and surrounding T cells, up-regulated CD40L expression on normal B cells. CONCLUSIONS. Thus, the expression of CD40L and CD30L on the B cells of HID patients suggests that B lymphocytes may play a role in the regulation of H/RS cell growth in vivo. Depriving H/RS cells from CD30L and CD40L survival signals by eliminating B cells from HID lesions may be of therapeutic value.