CD4CD25 Regulatory Lymphocytes Induce Regression of Intestinal Tumors in Apc Mice
نویسندگان
چکیده
Colorectal cancer in humans results from sequential genetic changes in intestinal epithelia commencing with inactivation of the APC tumor suppressor gene. Roles for host immunity in epithelial tumorigenesis are poorly understood. It has been previously shown that CD4CD25 lymphocytes inhibit colitisassociated epithelial tumors in Rag-deficient mice. Here we show that addition of CD4CD25 lymphocytes in Apc mice reduces multiplicity of epithelial adenomas. Interleukin10 was required in regulatory cells for therapeutic effect. Recipients of regulatory cells showed increased apoptosis and down-regulation of cyclooxygenase-2 within tumors coincident with tumor regression. These data suggest a role for regulatory lymphocytes in epithelial homeostasis in the Apc mouse model of intestinal polyposis. Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans. (Cancer Res 2005; 65(10): 3998-4004)
منابع مشابه
Award Number: W81XWH-05-1-0460 TITLE: Are Anti-inflammatory Lymphocytes Able to Induce Remission of Breast Cancer PRINCIPLE INVESTIGATOR:
Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to be a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4CD45RB (TE) cells to induce inflammatory bowel di...
متن کاملProinflammatory CD4CD45RB Lymphocytes Promote Mammary and Intestinal Carcinogenesis in Apc Mice
Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to be a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4CD45RB (TE) cells to induce inflammatory bowel di...
متن کاملRegulatory CD 4 + CD 25 + cells reverse imbalances in the T cell pool of bone marrow transplanted TG e 26 mice leading to the prevention of colitis
Background and aims: Erroneous thymic selection of developing T lymphocytes may be responsible for the expansion of self reactive T cells or may contribute to the absence of regulatory T cells important in controlling peripheral inflammatory processes. Colitis in bone marrow (BM) transplanted Tge26 mice is induced by abnormally activated T cells developing in an aberrant thymic microenvironment...
متن کاملSpontaneous Intestinal Tumorigenesis in Apc/Min+ Mice Requires Altered T Cell Development with IL-17A
The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc (/Min+) mouse model that resembles human familial adenomatous polyposis (FAP). Apc (/Min+) mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lam...
متن کاملMolecular signature of recent thymic selection events on effector and regulatory CD4 T lymphocytes Running title: Thymic selection of effector and regulatory CD4 T lymphocytes
Natural CD4CD25 regulatory T lymphocytes are key protagonists in induction and maintenance of peripheral T cell tolerance. Their thymic origin and biased repertoire continue to raise important questions on the signals that mediate their development. We validated analysis of MHC class II-capture by developing thymocytes from thymic stroma as a tool to study quantitative and qualitative aspects o...
متن کامل