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 dev elopment, Recombinase-activating gene CRAG)-1, RAG-2 and pre-TCR-a expressi on in the normal adult human liver (AHL), together,vith the presence of lym phoid-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 transcripta se polymerase chain reaction was used to detect IL-7 using primers that amp lified 620 base pair (bp) fragments and other smaller transcripts. A sandwi ch enzyme-linked immunosorbent assay was developed to quantify IL-7 protein in homogenates. The anatomic distribution of IL-7-secreting cells was dete rmined by immunohistochemistry. IL-7-specific product (620 bp) was detected in nine of ten samples, with six also positive for a smaller splice-varian t (488 bp), Levels of the 620 bp product were 2.5 times greater than the 48 8 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 discre te cells of lymphoid morphology, widely distributed throughout the parenchy ma 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 t he normal AHL is a suitable microenvironment for T cell differentiation. (C ) 2001 Academic Press.