EXPRESSION OF INTERLEUKIN 7 (IL-7) mRNA AND PROTEIN IN THE NORMAL ADULT HUMAN LIVER: IMPLICATIONS FOR EXTRATHYMIC T CELL DEVELOPMENT

Abstract

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-α 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 (620bp) was detected in nine of ten samples, with six also positive for a smaller splice-variant (488bp). Levels of the 620bp product were 2.5 times greater than the 488bp fragment. IL-7 protein was detected in all samples (range 18.47–76.93pg/100mg 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.