Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs

Dan Li, Yufeng Li, Jessica A. Hernandez, Rebecca Patenia, Tae Kon Kim, Jahan Khalili, Mark C. Dougherty, Patrick J. Hanley, Catherine M. Bollard, Krishna V. Komanduri, Patrick Hwu, Richard E. Champlin, Laszlo G. Radvanyi, Jeffrey J. Molldrem, Qing Ma

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Statin treatment has been shown to reduce graft-versus-host disease while preserving graft-versus-tumor effect in allogeneic stem cell transplantation. Herein, we investigated whether lovastatin treatment affects the function of human cytolytic T lymphocytes (CTLs). Upon T-cell receptor stimulation, lovastatin significantly inhibited the proliferation of both CD4+ and CD8+ T cells from healthy donors whereas their intracellular cytokine production including interferon-γ and tumor necrosis factor-α remained the same with a slight decrease of interleukin-2. Moreover, the specific lysis of target cells by CTL lines derived from patients and normal donors specific for Epstein-Barr virus-encoded antigen latent membrane protein-2 or cytomegalovirus-encoded antigen pp65 was uncompromised in the presence of lovastatin. In addition, we evaluated the effect of lovastatin on the proliferation and effector function of the CD8+ tumor-infiltrating lymphocytes (TILs) derived from melanoma patients specific for MART-1 antigen. Lovastatin significantly reduced the expansion of antigen-specific TILs upon MART-1 stimulation. However, the effector function of TILs, including the specific lysis of target cells and secretion of cytokine interferon-γ, remained intact with lovastatin treatment. Taken together, these data demonstrated that lovastatin inhibits the proliferation of Epstein-Barr virus, cytomegalovirus, and MART-1-specific CTLs without affecting cytolytic capacity. The differential effect of lovastatin on the proliferation versus cytoxicity of CTLs might shed some light on elucidating the possible mechanisms of graft-versus-host disease and graft-versus-tumor effect elicited by alloimmune responses.

Original languageEnglish (US)
Pages (from-to)975-982
Number of pages8
JournalJournal of Immunotherapy
Volume33
Issue number9
DOIs
StatePublished - Nov 1 2010

Keywords

  • cytolytic T lymphocytes (CTLs)
  • cytotoxicity
  • proliferation
  • statin
  • tumorinfiltrating lymphocytes (TILs)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

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    Li, D., Li, Y., Hernandez, J. A., Patenia, R., Kim, T. K., Khalili, J., Dougherty, M. C., Hanley, P. J., Bollard, C. M., Komanduri, K. V., Hwu, P., Champlin, R. E., Radvanyi, L. G., Molldrem, J. J., & Ma, Q. (2010). Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs. Journal of Immunotherapy, 33(9), 975-982. https://doi.org/10.1097/CJI.0b013e3181fb0486