Cell dynamics and expression of tumor necrosis factor (TNF)-α, interleukin-6, and TNF receptors in angioimmunoblastic lymphadenopathy-type T cell lymphoma

Abstract Angioimmunoblastic lymphadenopathy (AILD)-type T cell lymphoma is histologically characterized by a mixed infiltrate of atypical T cells and B cells including B immunoblasts and plasma cells as well as eosinophils accompanied by proliferation of high endothelial venules. These morphological peculiarities are widely believed to reflect an abnormal pattern of cytokine expression. To clarify the cell dynamics and cytokine expression pattern in the lymph nodes of AILD-type T cell lymphoma, the frequency of proliferating/apoptotic cells and localization of tumor necrosis factor (TNF)-α and interleukin (IL)-6 producing cells were determined. Double staining was performed for (1) cell markers and Ki-67 antigen, (2) cell markers and the terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) method, or (3) cell markers and cytokines. The proliferating cell ratio in atypical T cells of AILD-type T cell lymphoma determined by Ki-67 labeling was 20.2 ± 5.0%, while other peripheral T cell lymphomas (PTL) exhibited a ratio of 32.9 ± 2.5%. TUNEL-positive apoptotic cells were 0.8 ± 0.1% of total cells in AILD-type T cell lymphoma. They were dominantly atypical cells with positive T cell markers. In contrast, lymphoma cells in other types of PTL or paracortical cells in reactive follicular hyperplasia had only 0.3 ± 0.1 or 0.4 ± 0.1% TUNEL-positive cells, respectively. Thus, lymphoma cells in AILD-type T cell lymphoma demonstrated suppressed proliferating activity and enhanced apoptosis when compared to other types of PTL. TNF-α-producing cells were observed in all of the lymph nodes from AILD-type T cell lymphoma cases (15/15) and positive staining was obtained in the majority of atypical T cells and scattered macrophages. In contrast, IL-6 was localized to clusters of atypical T cells in some of the cases (9/15). Further, the expression of TNF-α, IL-6, and TNF receptors I and II (TNFRI and TNFRII) was examined by RT-PCR. The TNF-α message (2/2) and IL-6 message (2/2) was present in the lymph nodes of AILD-type T cell lymphoma by examination using RT-PCR, while both messages were negative in control cases (0/7). As far as an expression of mRNA for TNF receptors in AILD-type T cell lymphoma cases, mRNA for TNFRI was definitely expressed in both of the cases (2/2) while TNFRII mRNA was weakly expressed in one case (1/2). Overexpression of TNF-α as well as TNFRI may play a role in controlling T cell proliferation through an autocrine (T cell–T cell interaction) and paracrine (macrophage–T cell interaction) fashion. IL-6, which was also expressed by part of lymphoma cells of AILD-type T cell lymphoma, facilitates the proliferation of B cells, plasma cells, and T cells or endothelial cells in the lymph nodes of AILD-type T cell lymphoma.