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Patterns of cytokine gene expression in peripheral T-cell lymphoma of
angioimmunoblastic lymphadenopathy type
HD Foss, I Anagnostopoulos, H Herbst, M Grebe, K Ziemann, M Hummel and H Stein
Konsultations- und Referenzzentrum fur Lymphknoten und Hamatopathologie,
Institute of Pathology, Klinikum Benjamin Franklin, Free University of
Berlin, Germany.
Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type
(AILD-TCL) is histologically characterized by a mixed infiltrate of
atypical T cells, B cells including B immunoblasts, and plasma cells, as
well as eosinophilic granulocytes accompanied by proliferated high
endothelial venules, while, clinically, fever and weight loss are often
observed. These morphologic and clinical pecularities are widely believed
to reflect abnormal patterns of cytokine expression. To evaluate this
hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of
tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6),
and IL-1 beta transcripts by in situ hybridization (ISH) using
[35S]-labeled cytokine-specific RNA probes in seven cases subsequent to
immunohistology for cell type characteristic antigens. Expression of all
four cytokines was strongly enhanced in AILD-TCL when compared with the
control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas,
other than AILD-TCL. TNF and LT transcripts were present in atypical T
cells and in a variable proportion of B immunoblasts in all AILD-TCL cases,
whereas IL-6 and IL- 1 beta specific transcripts were mainly found in
nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr
virus (EBV)- infected cells, which are frequently present in AILD-TCL, the
detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for
cytokine transcripts. It became evident that expression of LT and TNF by
EBV- infected cells was largely restricted to B immunoblasts, which were
only infrequently present in most AILD-TCL cases, whereas the expression of
IL-6 was very rare, and IL-1 beta was not found in EBV- infected cells.
These data suggest that expression of TNF and LT genes may contribute to
the characteristic histologic and clinical features of AILD-TCL and that
cytokine expression by EBV-infected cells does not, in most cases,
contribute significantly to the overall cytokine expression. Because it has
been shown that LT is an autocrine growth factor for EBV-infected B cells,
expression of this cytokine could contribute to the proliferation of
EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression,
may ultimately play a role in the development of B-immunoblastic lymphomas.
Volume 85,
Issue 10,
pp. 2862-2869,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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