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

Clinical and Experimental Immunology - Tập 138 Số 1 - Trang 94-101 - 2004
Lucy Golden‐Mason1,2, Anna M. Kelly3,1, Derek G. Doherty4, O. Traynor3, Gerry McEntee3, Jacinta Kelly2, John E. Hegarty5,3, Cliona O’Farrelly5,1
1Education and Research Centre
2National Liver Transplant Unit, St Vincent's University Hospital, Dublin
3Dublin Institute of Technology
4Institute of Immunology and Department of Biology, National University of Ireland, Maynooth, Co. Kildare
5Conway Institute, University College, Dublin, Ireland

Tóm tắt

SUMMARYInterleukin 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.

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Clinical and Experimental Immunology

Tập 138 Số 1

94-101

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