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Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's
disease cell lines
A Carbone, A Gloghini, V Gattei, D Aldinucci, M Degan, P De Paoli, V Zagonel and A Pinto
Division of Pathology, Istituto Nazionale di Ricovero e Cura a Carattere
Scientifico, Aviano, Italy.
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.
Volume 85,
Issue 3,
pp. 780-789,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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