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

Jun An, Hiroshi Fujiwara, Koichiro Suemori, Toshiyuki Niiya, Taichi Azuma, Kazushi Tanimoto, Toshiki Ochi, Yoshiki Akatsuka, Junichi Mineno, Hidetoshi Ozawa, Fumihiko Ishikawa, Kiyotaka Kuzushima, Masaki Yasukawa

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Abstract

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 WT1235-243-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.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalInternational Journal of Hematology
Volume93
Issue number2
DOIs
Publication statusPublished - 01-02-2011

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All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

An, J., Fujiwara, H., Suemori, K., Niiya, T., Azuma, T., Tanimoto, K., Ochi, T., Akatsuka, Y., Mineno, J., Ozawa, H., Ishikawa, F., Kuzushima, K., & Yasukawa, M. (2011). Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis. International Journal of Hematology, 93(2), 176-185. https://doi.org/10.1007/s12185-010-0758-7