Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice

Marsh, Lorraine, Coletta, P Louise, Hull, Mark A, Selby, Peter J and Carding, Simon R (2012) Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice. International Journal of Oncology, 40 (1). pp. 243-50. ISSN 1019-6439

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ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length of the small intestine and colon. Currently little is known about the role of the immune system in regulating intestinal tumorigenesis in these animals. This study characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect that T cells expressing either γδ or αβ encoded T cell receptors (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme-mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared with wild-type IELs. Analysis of ApcMin/+ mice crossed with αβ T-cell deficient (TcRβ-/-) or γδ T-cell deficient (TcRδ-/-) mice on the same genetic background revealed decreased tumour multiplicity in the absence of both αβ and γδ T-cells. This study demonstrates that altered T-cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and forms the basis for future mechanistic studies.

Item Type: Article
Uncontrolled Keywords: adenoma,adenomatous polyposis coli protein,animals,cell transformation, neoplastic,female,intestinal mucosa,intestinal neoplasms,intestine, small,lymphocytes,male,mice,mice, inbred c57bl,receptors, antigen, t-cell, alpha-beta,receptors, antigen, t-cell, gamma-delta,t-lymphocyte subsets
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Pure Connector
Date Deposited: 06 Jan 2014 15:16
Last Modified: 24 Oct 2022 05:29
DOI: 10.3892/ijo.2011.1176

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