Hepatic interleuklin 15 (IL-15) expression: implications for local NK/NKT cell homeostasis and development

Clin Exp Immunol. 2004 Oct;138(1):94-101. doi: 10.1111/j.1365-2249.2004.02586.x.


Interleukin 15 (IL-15) is critical for the development of human and murine natural killer (NK) cells and hepatic-derived NK T cells (NKT) in mice, and for the homeostatic maintenance of NK/NKT and CD8(+) memory T cells. The lymphocyte repertoire of an adult human liver includes significant populations of NK and NKT-like cells, which may arise locally from hepatic haematopoietic stem cells (HSCs). We investigated hepatic IL-15 levels and the expression of IL-2/IL-15-receptor beta-chain (IL-2/IL-15Rbeta; CD122) on mature hepatic lymphocytes and HSCs. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect secreted/intracellular IL-15 transcripts. IL-15 protein was localized using immunohistochemistry; levels were measured by enzyme-linked immunosorbent assay IL-2/IL-15Rbeta expression by flow-cytometry. Normal hepatic IL-15 protein was detected at 0.43 ng/100 mg total protein (n = 11, range 0.10 ng-0.9 ng). There was a significant increase in HCV-infected tissue (1.78 ng, P < 0.005, n = 11, range 0.18-2.43 ng). The staining pattern suggests that infiltrating monocytes and tissue resident Kupffer cells are the main producers. IL-15 protein was detected in supernatants from cultured liver biopsy specimens in the absence of stimulation (mean 175.8 pg/100 mg wet tissue, n = 3), which increased significantly upon stimulation (P < 0.05, mean 231.21 pg). On average, 61% of hepatic HSCs expressed IL-2/IL-15Rbeta suggesting a local lymphopoietic role. Eighty per cent of NK and 45.8% of CD56(+) T cells expressed IL-2/IL-15Rbeta, suggesting involvement in local CD56(+) cell activation and expansion. Constitutive expression of IL-15 protein and IL-2/IL-15Rbeta on hepatic lymphocytes suggests a key role in the generation and maintenance of the unique hepatic lymphoid repertoire. The significant increase observed in HCV-infected liver suggests a role for IL-15 in host antiviral responses in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / immunology
  • Female
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-15 / analysis*
  • Interleukin-2 / analysis
  • Killer Cells, Natural / immunology*
  • Liver / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, Interleukin-2 / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Interleukin-15
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2