| First Author | Lúdvíksson BR | Year | 1997 |
| Journal | J Immunol | Volume | 159 |
| Issue | 7 | Pages | 3622-8 |
| PubMed ID | 9317162 | Mgi Jnum | J:110678 |
| Mgi Id | MGI:3640874 | Doi | 10.4049/jimmunol.159.7.3622 |
| Citation | Ludviksson BR, et al. (1997) TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice. J Immunol 159(7):3622-8 |
| abstractText | 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. |
