Transfer of colitis by Galphai2-deficient T lymphocytes: impact of subpopulations and tissue origin.
To elucidate the potential cell population(s) involved in the induction of colitis in inhibitory G protein Galphai2(-/-) mice, Galphai2-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-gamma was measured using ELISA. After adoptive transfer of Galphai2(-/-) bone marrow, severe colitis developed in irradiated wild type recipients, whereas irradiated Galphai2(-/-) mice increased their life span more than 3 times after transfer of wild type bone marrow, accompanied by significant amelioration of colitis. Neither purified Galphai2(-/-) 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 Galphai2(-/-) CD3(+) T cells induced severe colitis. In contrast, transfer of Galphai2(-/-) CD3(+) T cells from the MLN caused only minor histopathological changes in the intestinal mucosa. Finally, serum levels of interleukin-18 and interferon-gamma production from colonic tissue cultures correlated well with disease severity. Our results show that bone marrow transplantation can prolong the life of Galphai2(-/-) 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.
Bjursten
Malin
M
Department of Clinical Immunology, Göteborg University, Gothenburg, Sweden.
Willén
Roger
R
Hultgren Hörnquist
Elisabeth
E
D000818:Animals; D017252:CD3 Complex; D003092:Colitis / Q000276:immunology* / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics* / Q000502:physiology*; D007121:Immunocompetence; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D016207:Cytokines; D051960:GTP-Binding Protein alpha Subunit, Gi2