Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing
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Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing. / Kjellev, Stine; Lundsgaard, Dorthe; Poulsen, Steen Seier; Markholst, Helle.
In: International Immunopharmacology, Vol. 6, No. 8, 01.08.2006, p. 1341-54.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing
AU - Kjellev, Stine
AU - Lundsgaard, Dorthe
AU - Poulsen, Steen Seier
AU - Markholst, Helle
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice reconstituted with syngeneic CD25-depleted CD4+ cells, including the identification of useful biomarkers, and assessment of the similarities to IBD with focus on the relationship between colonic epithelial proliferation and inflammatory parameters. Groups of reconstituted and un-reconstituted mice were sacrificed weekly from week 1 to 4. Clinical signs of colitis occurred approximately 2 weeks after reconstitution. Disease onset and severity based on histopathology correlated well with the colonic weight:length ratio, fecal consistency score, presence of occult blood in feces, and fecal IL-1beta content. Loss in body weight was not apparent until colitis was well established and exhibited lower coefficient of correlation to the histologic score. Early colonic histopathology was dominated by epithelial hyperproliferation, loss of mucus and mild lymphoid infiltration. Epithelial hyperproliferation was paralleled by increased fecal soluble tumor necrosis factor receptor II content. Cytokines in colonic tissue homogenates exhibited a Th1-like profile. We conclude that adoptive transfer of CD4+CD25- T cells results in colitis resembling IBD with a rapid onset and limited variability between individuals. Purification of CD4+CD25- T cells is a simple procedure, and does not require flow-cytometric sorting. Fecal consistency score and colonic weight:length ratio are readily measurable and consistent disease parameters. This model is thus highly suitable for pharmacological testing of intervention strategies.
AB - Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice reconstituted with syngeneic CD25-depleted CD4+ cells, including the identification of useful biomarkers, and assessment of the similarities to IBD with focus on the relationship between colonic epithelial proliferation and inflammatory parameters. Groups of reconstituted and un-reconstituted mice were sacrificed weekly from week 1 to 4. Clinical signs of colitis occurred approximately 2 weeks after reconstitution. Disease onset and severity based on histopathology correlated well with the colonic weight:length ratio, fecal consistency score, presence of occult blood in feces, and fecal IL-1beta content. Loss in body weight was not apparent until colitis was well established and exhibited lower coefficient of correlation to the histologic score. Early colonic histopathology was dominated by epithelial hyperproliferation, loss of mucus and mild lymphoid infiltration. Epithelial hyperproliferation was paralleled by increased fecal soluble tumor necrosis factor receptor II content. Cytokines in colonic tissue homogenates exhibited a Th1-like profile. We conclude that adoptive transfer of CD4+CD25- T cells results in colitis resembling IBD with a rapid onset and limited variability between individuals. Purification of CD4+CD25- T cells is a simple procedure, and does not require flow-cytometric sorting. Fecal consistency score and colonic weight:length ratio are readily measurable and consistent disease parameters. This model is thus highly suitable for pharmacological testing of intervention strategies.
KW - Adoptive Transfer
KW - Animals
KW - Antigens, CD11c
KW - Antigens, CD4
KW - CD4-Positive T-Lymphocytes
KW - Colitis
KW - Colon
KW - Cytokines
KW - Disease Models, Animal
KW - Epithelium
KW - Female
KW - Goblet Cells
KW - Immunohistochemistry
KW - In Situ Hybridization
KW - Inflammation
KW - Inflammation Mediators
KW - Intestinal Mucosa
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, SCID
KW - Occult Blood
KW - Peptides
KW - Receptors, Interleukin-2
U2 - 10.1016/j.intimp.2006.04.017
DO - 10.1016/j.intimp.2006.04.017
M3 - Journal article
C2 - 16782548
VL - 6
SP - 1341
EP - 1354
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 8
ER -
ID: 33792937