Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodgkin disease

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Abstract
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 HD 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 HD 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 HD lesions may be of therapeutic value. Cancer 2002;94:1–5. © 2002 American Cancer Society.