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

A M Williams, C V Whiting, K Bonhagen, J Reimann, S Bregenholt, Mogens Helweg Claesson, P W Bland

12 Citations (Scopus)

Abstract

The adoptive transfer of activated CD4+ alpha/beta 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-alpha. 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-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages transcribing and translating TNF-alpha were clustered in areas of tissue destruction. Crypt epithelium of inflamed tissues transcribed TNF-alpha at a very early stage of the disease process, but translation of TNF-alpha protein could only be found in advanced epithelial dysplasia. This indicates differential post-transcriptional control of TNF-alpha in activated macrophages and the epithelium.
Original languageEnglish
JournalClinical and Experimental Immunology
Volume116
Issue number3
Pages (from-to)415-24
Number of pages10
ISSN0009-9104
Publication statusPublished - 1 Jun 1999

Keywords

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes
  • Colitis
  • Disease Models, Animal
  • Macrophage Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Protein Biosynthesis
  • RNA, Messenger
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha

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