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Keywords:

  • human;
  • lymphopoiesis ;
  • NK cells;
  • normal liver;
  • stem cells

SUMMARY

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 β-chain (IL-2/IL-15Rβ ; 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-15Rβ 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-15Rβ suggesting a local lymphopoietic role. Eighty per cent of NK and 45·8% of CD56+ T cells expressed IL-2/IL-15Rβ, suggesting involvement in local CD56+ cell activation and expansion. Constitutive expression of IL-15 protein and IL-2/IL-15Rβ 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.