Transfer of colitis by Gαi2‐deficient T lymphocytes: Impact of subpopulations and tissue origin

• Published in: Inflammatory bowel diseases Vol. 11; no. 11; pp. 997 - 1005
• Main Authors: Bjursten, Malin, Willén, Roger, Hörnquist, Elisabeth Hultgren
• Format: Journal Article
• Language: English
• Published: Philadelphia Lippincott Williams & Wilkins, Inc 01.11.2005
• Subjects: colitis; Gαi2−/− mice; interleukin‐18; irradiation; T‐cell transfer
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/01.MIB.0000185401.27170.22

To elucidate the potential cell population(s) involved in the induction of colitis in inhibitory G protein Gαi2−/− mice, Gαi2‐deficient or competent bone marrow or splenic and mesenteric lymph node (MLN) T cells were transferred into immunodeficient mice. The mice were followed up to 23 weeks after transfer, recording changes in body weight. Colitis was graded on hematoxylin and eosin‐stained colonic tissue, and production of serum interleukin‐18 and colon‐derived interferon‐γ was measured using ELISA. After adoptive transfer of Gαi2−/− bone marrow, severe colitis developed in irradiated wild type recipients, whereas irradiated Gαi2−/− mice increased their life span more than 3 times after transfer of wild type bone marrow, accompanied by significant amelioration of colitis. Neither purified Gαi2−/− CD4+, nor CD8+ splenic or MLN‐derived T cells could induce colitis in recombination‐activating gene V(RAG) 2−/− recipient mice, whereas transfer of splenic Gαi2−/− CD3+ T cells induced severe colitis. In contrast, transfer of Gαi2−/− CD3+ T cells from the MLN caused only minor histopathological changes in the intestinal mucosa. Finally, serum levels of interleukin‐18 and interferon‐γ production from colonic tissue cultures correlated well with disease severity. Our results show that bone marrow transplantation can prolong the life of Gαi2−/− mice and ameliorate intestinal inflammation. Splenic CD4+ or CD8+ T cells on their own were poor inducers of colitis, whereas the combination of both was highly involved in the induction of intestinal inflammation. Furthermore, we show that the tissue origin of CD3+ T cells is critical for their potency to induce colitis.