CD8+ cytotoxic T cells induce relapsing colitis in normal mice.
Gastroenterology
; 131(2): 485-96, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16890603
ABSTRACT
BACKGROUND & AIMS:
Most mouse models of IBD have emphasized an effector role of type-1 CD4+ T cells in colitis. The aim of this study was to develop a model of antigen-specific relapsing colitis to investigate the relative contribution of CD4+ and CD8+ effectors.METHODS:
Balb/C mice were sensitized and challenged with a suboptimal dose of 2.4 dinitrobenzene sulfonic acid to generate a colonic delayed-type hypersensitivity response. The respective role of CD4+ and CD8+ T cells in the initiation of colitis was analyzed by in vivo monoclonal antibody depletion and cell-transfer experiments. Dynamic and function of the colitogenic effectors were studied by immunohistochemistry, fluorescence-activated cell sorter analysis, enzyme-linked immunospot assay, quantitative polymerase chain reaction, and in vivo CTL assays.RESULTS:
Relapsing colitis rapidly occurred only after challenge of previously sensitized mice. Interferon-gamma-producing cytotoxic CD8+ T cells (Tc1) specific for hapten-modified self-proteins were generated in colon-draining lymph nodes on day 5 after sensitization, before the onset of disease. These CD8+ T cells were rapidly recruited upon challenge into colon lamina propria as granzyme B-expressing effectors exerting ex vivo cytotoxicity against syngeneic hapten-modified colonic epithelial cells. Colitis was prevented by in vivo antibody depletion of CD8+, but not of CD4+, T cells and could be induced in naive recipients within 48 hours after transfer of CD8+, but not CD4+, T cells purified from sensitized mice.CONCLUSIONS:
Our data show that antigen-specific CD8+ T cells can induce relapsing colitis in normal mice and suggest that the cytolytic function of CD8 Tc1 against epithelial cells may initiate the intestinal inflammatory process.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Colite
/
Linfócitos T CD8-Positivos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
França