TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice.

Abstract

A severe, Th1-mediated experimental colitis with similarities to inflammatory bowel disease in humans can be induced by a single injection of 2,4,6-trinitrophenol (TNP)-substituted protein plus adjuvant in IL-2-/- mice. To determine the early events involved in the pathogenesis of IL-2-/-colitis, we compared the function of lamina propria (LP) T cells from IL-2-/- and IL-2+/+ mice subjected to disease-inducing (TNP-conjugated keyhole limpet hemocyanin [TNP-KLH]) and disease-inhibiting (anti-CD3) immunization protocols. We show that LP T cells in TNP-KLH-immunized IL-2-/- mice fail to produce TGF-beta early (day 2), whereas LP T cells in TNP-KLH-immunized IL-2+/+ mice exhibit an approximately eightfold rise in TGF-beta secretion. The critical importance of local TGF-beta production was further substantiated by the following findings. 1) LP T cells from TNP-KLH-immunized IL-2-/- mice administered anti-CD3 (i.p.) exhibit a significant rise in TGF-beta, production but fail to produce IFN-gamma, and such mice do not develop colitis. 2) TNP-KLH-immunized IL-2-/- mice administered anti-CD3 and coadministered anti-TGF-beta mAb again give rise to IFN-gamma-producing LP cells, and such mice develop colitis. 3) TNP-KLH-immunized IL-2+/+ mice administered anti-TGF-beta mAb exhibit pockets of mononuclear cell infiltrates in the LP. These results indicate that the disposition of IL-2-/- mice to develop chronic colonic inflammation is due to a Th1 cell response in the LP that is not appropriately counter-regulated by the production of the suppressor cytokine, TGF-beta.

• Authors: B R Lúdvíksson, R O Ehrhardt, W Strober
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 159 Issue 7 Pg. 3622-8 (Oct 01 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9317162 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• CD3 Complex
• Haptens
• Interleukin-2
• Picrates
• Transforming Growth Factor beta
• trinitrophenyl keyhole limpet hemocyanin
• Interleukin-4
• Hemocyanins
• picric acid

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• CD3 Complex (immunology)
• Colitis (etiology, immunology, prevention & control)
• Female
• Haptens
• Hemocyanins (immunology, metabolism)
• Interleukin-2 (deficiency, genetics)
• Interleukin-4 (biosynthesis, deficiency)
• Male
• Mice
• Mice, Knockout
• Picrates (immunology)
• Th1 Cells (immunology)
• Transforming Growth Factor beta (antagonists & inhibitors, biosynthesis, deficiency)