PATTERNS OF CYTOKINE GENE-EXPRESSION IN PERIPHERAL T-CELL LYMPHOMA OFANGIOIMMUNOBLASTIC LYMPHADENOPATHY TYPE

Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of a typical T cells, B cells including B immunoblasts, and plasma cells, a s well as eosinophilic granulocytes accompanied by proliferated high e ndothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely beli eved to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the pre sence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleu kin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [S-35]-labeled cytokine-specific RNA probes in seven cases subs equent to immunohistology for cell type characteristic antigens. Expre ssion of all four cytokines was strongly enhanced in AILD-TCL when com pared with the control groups of lymphoblastic lymphomas and periphera l T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were p resent in atypical T cells and in a variable proportion of B immunobla sts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcr ipts were mainly found in nonlymphoid cells. To verify a possible cyto kine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear R NAs (EBER) was combined with ISH for cytokine transcripts. It became e vident 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, an d IL-1 beta was not found in EBV-infected cells. These data suggest th at expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expres sion by EBV-infected cells does not, in most cases, contribute signifi cantly to the overall cytokine expression. Because it has been shown t hat LT is an autocrine growth factor for EBV-infected B cells, express ion of this cytokine could contribute to the proliferation of EBV-infe cted B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphoma s. (C) 1995 by The American Society of Hematology.