DNA aneuploidy in ulcerative colitis

Abstract

Administration of anti-CD25 mAb before an aggressive murine breast tumor inoculation provoked effective antitumor immunity. Compared with CD4⁺ T cells purified from anti-CD25 mAb-pretreated mice that did not reject tumor, CD4⁺ T cells purified from anti-CD25 mAb-pretreated mice that rejected tumor stimulated by dendritic cells (DCs) produced more IFN-γ and IL-2, and less IL-17 in vitro, and ignited protective antitumor immunity in vivo in an adoptive transfer model. Tumor Ag-loaded DCs activated naive CD8⁺ T cells in the presence of these CD4⁺ T cells in vitro. Tumor Ag and adoptively transferred CD4⁺ T cells were both required for inducing a long-term tumor-specific IFN-γ-producing cellular response and potent protective antitumor activity. Although adoptively transferred CD4⁺ T cells ignited effective tumor-specific antitumor immunity in wild-type mice, they failed to do so in endogenous NK cell-depleted, Gr-1⁺ cell-depleted, CD40^−/−, CD11c⁺ DC-depleted, B cell^−/−, CD8⁺ T cell-depleted, or IFN-γ^−/− mice. Collectively, the data suggest that adoptively transferred CD4⁺ T cells orchestrate both endogenous innate and adaptive immunity to generate effective tumor-specific long-term protective antitumor immunity. The data also demonstrate the pivotal role of endogenous DCs in the tumor-specific protection ignited by adoptively transferred CD4⁺ T cells. Thus, these findings highlight the importance of adoptively transferred CD4⁺ T cells, as well as host immune components, in generating effective tumor-specific long-term antitumor activity.