Tumour necrosis factor-alpha (TNF-α) transcription and translation in the CD4+ T cell-transplanted scid mouse model of colitis

Abstract

Abstract The adoptive transfer of activated CD4+α/β T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from recipient colon show a Th1 cytokine phenotype. We have examined the relationship between the phenotype of the cellular infiltrate and the transcription and translation of the proinflammatory cytokine TNF-α. The techniques of double indirect immunohistology and in situ hybridization using digoxigenin-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-α transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages transcribing and translating TNF-α were clustered in areas of tissue destruction. Crypt epithelium of inflamed tissues transcribed TNF-α at a very early stage of the disease process, but translation of TNF-α protein could only be found in advanced epithelial dysplasia. This indicates differential post-transcriptional control of TNF-α in activated macrophages and the epithelium.