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

The adoptive transfer of activated CD4(+) alpha/beta T cell blasts from the spleens of immunocompetent C.B- 17(+/+) or BALB/c(dm2) mice into C.B-17(sc id/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 relati onship between the phenotype of the cellular infiltrate and the transcripti on and translation of the proinflammatory cytokine TNF-alpha. The technique s of double indirect immunohistology and in situ hybridization using digoxi genin-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80(+), Mac-1(+) macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and tran slation were associated with activated macrophages in the lamina propria. A ctivated macrophages transcribing and translating TNF-alpha were clustered in areas of tissue destruction. Crypt epithelium of inflamed tissues transc ribed TNF-alpha at a very early stage of the disease process, but translati on of TNF-alpha protein could only be found in advanced epithelial dysplasi a. This indicates differential post-transcriptional control of TNF-alpha in activated macrophages and the epithelium.