The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in gammadelta T cells in large intestinal mucosa.
OBJECTIVE
Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal gammadelta T cells.


METHODS
The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal gammadelta T cells were evaluated by flow cytometry.


RESULTS
CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-beta1 and no change in IFN-gamma serum levels. Increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal gammadelta T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes.


CONCLUSIONS
Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in gammadelta T cells in large intestinal mucosa.
Ye
Yuefang
Y
Department of Gastroenterology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China.
Jin
Xi
X
Yue
Min
M
Chen
Shaohua
S
Yu
Chaohui
C
Li
Youming
Y
D000284:Administration, Oral; D000818:Animals; D003092:Colitis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007108:Immune Tolerance; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007420:Intestine, Large / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014945:Wound Healing / Q000187:drug effects
D020011:Protective Agents; D011506:Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma