Altered T-Cell Balance in Lymphoid Organs of a Mouse Model of Colorectal Cancer

Scott M. Tanner, Joseph G. Daft, Stephanie A. Hill, Colin A. Martin, Robin G. Lorenz

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The adenomatous polyposis coli (APC) gene is a known tumor suppressor gene, and mice with mutations in Apc (ApcMin/+) spontaneously form multiple intestinal neoplasms. In this model of human colorectal cancer (CRC), it has been reported that CD4+ T-cell-derived interleukin 17 (IL-17) promotes intestinal tumor development, but it is not known if the Apc mutation actually directly alters T-cell function and subsequently tumor immunosurveillance. To investigate the ApcMin/+ mutation on T-cell function, flow cytometric, histochemical, and immunofluorescent studies on both wild-type (Apc+/+) and ApcMin/+ mice were performed. We identified decreased levels of interferon gamma (IFN-γ+)IL-17+ double-positive CD4+ cells in the mesenteric lymph nodes and Peyer’s patches of ApcMin/+ mice. In addition, altered levels of CD8+ cells, and changes in CD8+ production of IFN-γ and granzyme B were observed. These T-cell alterations did modify tumor immunosurveillance, as the adoptive transfer of splenocytes from ApcMin/+ animals into a chemically induced CRC model resulted in the inability to prevent epithelial dysplasia. These results suggest an altered T-cell balance in ApcMin/+ mice may disrupt intestinal homeostasis, consequently limiting intestinal tumor immunosurveillance.

Original languageEnglish
Pages (from-to)753-767
Number of pages15
JournalJournal of Histochemistry and Cytochemistry
Volume64
Issue number12
DOIs
StatePublished - 2016

Keywords

  • CD4
  • CD8
  • T cell
  • colorectal cancer
  • interferon gamma
  • interleukin 17
  • mouse model
  • mucosal immunity
  • tumor immunosurveillance

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