Expression of interleukin 7 (IL-7) mRNA and protein in the normal adult human liver: implications for extrathymic T cell development.
Interleukin-7 (IL-7) has been shown to play an essential role in T-cell development. Recombinase-activating gene (RAG)-1, RAG-2 and pre-TCR-alpha expression in the normal adult human liver (AHL), together with the presence of lymphoid-haematopoietic progenitors, is strong evidence that the AHL supports T cell maturation. We investigated IL-7 mRNA and protein levels in order to determine whether AHL could support T lymphocyte differentiation. Biopsies were snap frozen, powdered, and RNA/protein extracted. Reverse transcriptase polymerase chain reaction was used to detect IL-7 using primers that amplified 620 base pair (bp) fragments and other smaller transcripts. A sandwich enzyme-linked immunosorbent assay was developed to quantify IL-7 protein in homogenates. The anatomic distribution of IL-7-secreting cells was determined by immunohistochemistry. IL-7-specific product (620 bp) was detected in nine of ten samples, with six also positive for a smaller splice-variant (488 bp). Levels of the 620 bp product were 2.5 times greater than the 488 bp fragment. IL-7 protein was detected in all samples (range 18.47-76.93 pg/100 mg tissue). Immunohistochemistry demonstrated IL-7 protein in discrete cells of lymphoid morphology, widely distributed throughout the parenchyma and within portal tracts. Large populations of innate T cells are found in normal AHL, some of which may differentiate locally. The presence of IL-7 RNA and protein throughout normal hepatic tissue provides evidence that the normal AHL is a suitable microenvironment for T cell differentiation.
Golden-Mason
L
L
Education & Research Centre, St. Vincent's University Hospital, Dublin, Ireland.
Kelly
A M
AM
Traynor
O
O
McEntee
G
G
Kelly
J
J
Hegarty
J E
JE
O'Farrelly
C
C
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
D015851:Interleukin-7; D012333:RNA, Messenger