D-Limonene modulates T lymphocyte activity and viability

Cell Immunol. 2012 Sep;279(1):30-41. doi: 10.1016/j.cellimm.2012.09.002. Epub 2012 Sep 18.

Abstract

d-Limonene, a cyclic terpene that is a major component of several plant essential oils, is used widely as an additive in perfumes, soaps, foods and beverages, and has also been shown to possess chemopreventative and chemotherapeutic activity. A limited number of studies have been conducted investigating the effect of d-limonene on immune system function. We show that d-limonene and its metabolites limonene-1-2-diol and perillic acid inhibit the production by CD3(+)CD4(+) T cells of IFN-γ, IL-2, TNF-α, IL-4 and IL-13, and the production by CD3(+)CD8(+) T cells of IFN-γ, IL-2, and TNF-α. Additionally, the upregulation of CD25, CD69 and CD40L by activated T lymphocytes is modulated by d-limonene, limonene-1-2-diol and perillic acid treatment. Furthermore, high concentrations of d-limonene, limonene-1-2-diol and perillic acid induce T lymphocyte cell death. These data suggest that d-limonene possesses immunomodulatory activity that must be considered when utilizing the compound for therapeutic or commercial purposes.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cells, Cultured
  • Cyclohexenes / metabolism
  • Cyclohexenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Limonene
  • Mice
  • Mice, Inbred C57BL
  • Monoterpenes / pharmacology
  • Terpenes / metabolism
  • Terpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anticarcinogenic Agents
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Cyclohexenes
  • Interleukin-13
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Monoterpenes
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • Interleukin-4
  • perillic acid
  • Interferon-gamma
  • Limonene