title: Interleukin 12 (IL-12) is increased in tumour bearing human liver and expands CD8(+) and CD56(+) T cells in vitro but not in vivo.
abstract: Human liver is enriched with CD8(+)T- and CD3(+)CD56(+) natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56(+)/CD8(+)T lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n=13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n=9, 3678 pg, p< 0.01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8(+)T and CD3(+)CD56(+)NT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8(+)T and CD56(+)NT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes.
authors.affiliation: Education & Research Centre, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kelly
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.forename: Gerry
authors.initials: G
authors.lastname: McEntee
authors.forename: Oscar
authors.initials: O
authors.lastname: Traynor
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
authors.forename: John E
authors.initials: JE
authors.lastname: Hegarty
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
mesh_terms: D019002:CD56 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism*
chemical_list: D019002:CD56 Antigen; D007376:Interleukin-2; D018664:Interleukin-12