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.