Protective Effect of NK1.1+T Cells as Well as NK Cells against Intraperitoneal Tumors in Mice

Abstract

Peritoneal resident cells of mice normally contain small populations of NK cells and NK1.1+αβT cells. These populations increased after either 3LL or EL4 tumor inoculations into the peritoneal cavity.In vivodepletion of NK cell alone by anti-asialo GM1 (ASGM1) Ab significantly decreased survival time of tumor-injected mice, while depletion of both NK cells and NK1.1+T cells by anti-NK 1.1 Ab greatly shortened mouse survival time. NK1.1+T cells in peritoneal cavity consist of a larger proportion of double-negative T cells and smaller populations of CD4+T cells and Vβ8+T cells compared with liver NK1.1+T cells and normally lack Vβ2+T cells. Tumor inoculation induced rapid IL-12 and IFN-γ mRNA in tumor-infiltrating mononuclear cells (TIM). Although anti-NK1 Ab pretreatmentin vivoabrogated IFN-γ mRNA expression and IFN-γ production of TIM, NK cell depletion alone by anti-ASGM1 Ab pretreatment retained IFN-γ mRNA expression and partly inhibited IFN-γ production of TIM. Peritoneal NK cells as well as NK1.1+T cells but not NK1.1−T cells of 3LL cell- or EL4 cell-injected mice showed cytotoxicities against the same tumor cells. Further, either anti-IL-12 Ab or anti-IFN-γ Ab ip injection significantly shortened EL4 cell-inoculated mouse survival time. Our findings suggest that peritoneal macrophages activated by tumors produce IL-12 which activates NK cells and NK1.1+T cells to produce IFN-γ and both NK cells and NK1.1+T cells are important in suppressing the growth of the intraperitoneal tumors.