CD40 is a member of the
nerve growth factor receptor family, showing a significant homology to the
Hodgkin's disease (HD)-associated
antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312
lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC)
lymphomas, 141 cases of other non-Hodgkin's
lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of
paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed-Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC
lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other
lymphoma cells analyzed. Engagement of CD40 by its soluble
ligand (
CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by
interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/
CD40L adhesion pathway. Our data indicate that CD40 is a useful
antigen for immunodetection and identification of
tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with
cytokine-producing T lymphocytes.