Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis

• Published in: International journal of hematology Vol. 93; no. 2; pp. 176 - 185
• Main Authors: An, Jun, Fujiwara, Hiroshi, Suemori, Koichiro, Niiya, Toshiyuki, Azuma, Taichi, Tanimoto, Kazushi, Ochi, Toshiki, Akatsuka, Yoshiki, Mineno, Junichi, Ozawa, Hidetoshi, Ishikawa, Fumihiko, Kuzushima, Kiyotaka, Yasukawa, Masaki
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.02.2011; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Blood Cells - pathology; Cell Line, Tumor; Cytophagocytosis; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, T-Cell, Peripheral - pathology; Lymphoma, T-Cell, Peripheral - physiopathology; Lymphoma-associated hemophagocytic syndrome; Medical sciences; Medicine; Medicine & Public Health; Oncology; Original Article; Other diseases. Hematologic involvement in other diseases; Peripheral T-cell lymphoma; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; T-cell receptor signaling; Lymphoma-associated hemophagocytic syndrome; Peripheral T-cell lymphoma; T-cell receptor signaling; T cell receptor; Hematology; Malignant hemopathy; Lymphoid neoplasm; Histiocytosis; Non Hodgkin lymphoma; Peripheral T cell lymphoma; Hemophagocytic syndrome; Signal transduction; Lymphoproliferative syndrome; T-Lymphocyte; Cancer
• ISSN: 0925-5710; 1865-3774; 1865-3774
• DOI: 10.1007/s12185-010-0758-7

Peripheral T-cell lymphoma (PTCL) is a biologically diverse lymphoid malignancy. The clinical aggressiveness associated with hemophagocytic syndrome (HS) is a characteristic of PTCL, being more distinctive in CD8 + PTCL. However, the underlying mechanism of PTCL-associated HS has not yet been fully investigated. We newly established a novel IL-2-dependent CD8 + PTCL lymphoma cell line (T8ML-1) from a patient with CD8 + PTCL who suffered recurrent HS accompanying disease flare-up. Focusing on the lymphoma cell T-cell receptor (TCR), we examined the lymphoma cell functions responsible for such clinical manifestations. First, T8ML-1.1 in which endogenous TCR-α/β chains were silenced by siRNAs, and T8ML-1.2 in which endogenous TCR-α/β chains were replaced with HLA-A*24:02-restricted and WT1 235–243 -specific TCR-α/β, were established. T8ML-1 exerted phytohemagglutinin (PHA)-dependent cytotoxicity via granular exocytosis. Additionally, soluble factors produced by PHA-stimulated T8ML-1, which included INF-γ and TNF-α, but not by simple-cultured T8ML-1, caused human monocytes to exhibit erythrophagocytosis and thrombophagocytosis in vitro. PHA binding induced phosphorylation of CD3ζ chain. Furthermore, both cytotoxicity and hemophagocytosis were completely inhibited by T8ML-1.1, but eventually restored by T8ML-1.2. These data suggest that exogenous activation of TCR signaling in PTCL cells might play an important role in the formation of PTCL-associated HS.