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 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.
Clodi
Katharina
K
St. Anna Kinderspital, Vienna, Austria.
Asgari
Zahra
Z
Younes
Mamoun
M
Palmer
J Lynn
JL
Cabanillas
Fernando
F
Carbone
Antonino
A
Andreeff
Michael
M
Younes
Anas
A
D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D019013:CD40 Antigens; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4