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From the Département de Pathologie,*
Hôpital Henri Mondor, Créteil, France; Services d'Anatomie
Pathologique,
Hôpital Saint-Louis,
Paris, France; Hôpital Laennec,
Paris,
France; URA 1301 Institut Gustave Roussy,§
Villejuif, France; and Department of
Pathology,¶
University of Crete,
Heraklion, Greece
Several cytokines have been implicated in the pathogenesis of human
lymphomas. Among them, interleukin-10 (IL-10) is a pleiotropic
cytokine with various biological effects on B and T lymphocytes. Its
expression has been essentially studied in B-cell lymphomas,
where it appears to act as an autocrine growth factor. BCRF1 (also
called viral IL-10), an open reading frame of Epstein-Barr
virus, exhibits extensive sequence and functional homologies
with human IL-10. Some entities belonging to T- or natural killer
(NK)-cell lymphomas are characterized by a frequent association with
Epstein-Barr virus. We analyzed 39 cases of peripheral T-cell
lymphoma, as well as 7 cases of nasal NK-cell lymphoma,
for the presence of IL-10 transcripts by in situ
hybridization, to see whether this cytokine was expressed in
these tumors and whether its expression could be related to their
histological subtype and to the presence of Epstein-Barr virus. Because
the riboprobe used for in situ hybridization recognizes
both human and viral IL-10, 12 cases were also analyzed by
reverse transcription-polymerase chain reaction to verify the human or
viral origin of IL-10. It was found that 8 of 11 (73%) anaplastic
large cell lymphomas (ALCLs), 2 of 11 (18%) pleomorphic T-cell
lymphomas, and 3 of 7 (43%) nasal NK-cell lymphomas exhibited
a large number of IL-10-expressing cells, whereas only rare
scattered cells were detected in angioimmunoblastic (11 of 11) and in
T-cell lymphomas (6 of 6). In ALCLs, the pattern of
IL-10 mRNA-expressing cells showed an overlapping with the CD30
staining and preferential localization in sinusal and perifollicular
areas, thereby suggesting that IL-10-expressing cells were
tumor cells. Furthermore, IL-10 transcripts were detected in
the SU-DHL-1 anaplastic lymphoma cell line. No correlation with
Epstein-Barr virus profile was found, because all cases of ALCL
were negative for EBER 1 and 2 genes by in situ
hybridization. We confirmed the presence of human IL-10 mRNA by reverse
transcription-polymerase chain reaction in ALCLs as well as in NK-cell
lymphomas, whereas viral IL-10 was not detected. Thus,
human and not viral IL-10 is frequently expressed by tumor cells in
ALCLs and nasal NK-cell lymphomas. In view of its function in the
proliferation and the differentiation of cytotoxic T and NK
cells, and its immunosuppressive properties, IL-10 may
have a role in the pathogenesis of these
lymphomas.
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