CD4+CD25+ cell depletion from the normal CD4+ T cell pool prevents tolerance toward the intestinal flora and leads to chronic colitis in immunodeficient mice.
CD4+CD25+ regulatory T cells have been shown to prevent immune-mediated colitis in mice; however, it is unclear whether the absence of CD4+CD25+ in the normal CD4+ T cell pool is responsible for the development of chronic colitis. Using the T cell-deficient Tgepsilon26 mouse model, we show that CD4+CD25- cells but not CD4+CD25+ cells induce a severe intestinal inflammation. Transfer of CD4+CD25+ cells, together with CD4+CD25- cells, ameliorated intestinal inflammation, and reconstitution with the whole mesenteric lymph node cell pool did not induce colitis in recipients. Transferred CD4+CD25- cells were found mainly in the mesenteric lymph nodes, where they showed an activated TH1-like phenotype. In the absence of regulatory CD4+CD25+ T cells, recipient CD4 cells secreted IFN-gamma in response to stimulation with intestinal bacterial antigen that was prevented in vivo and in vitro by regulatory CD4+CD25+ cells. These studies suggest that CD4+CD25- cells have a strong colitogenic effect in the Tgepsilon26 colitis model and that CD4+CD25+ cells may be the main regulators that prevent or downregulate the proinflammatory effect of colitogenic T cells in the Tgepsilon26 mouse model.
Veltkamp
Claudia
C
Department of Gastroenterology, Ruprecht-Karls-University, Heidelberg, Germany. Claudia_veltkamp@med.uni-heidelberg.de
Ruhwald
Rebecca
R
Giesem
Thomas
T
Autschbach
Frank
F
Kaden
Ines
I
Veltkamp
Roland
R
Sartor
R Balfour
RB
Stremmel
Wolfgang
W
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D007108:Immune Tolerance; D016867:Immunocompromised Host; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008643:Mesentery / Q000276:immunology / Q000473:pathology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D015375:Receptors, Interleukin-2