title: Potent tumor-specific protection ignited by adoptively transferred CD4+ T cells.
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-gamma 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-gamma-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-gamma(-/-) 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.
authors.affiliation: Departments of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Zuqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Hae S
authors.initials: HS
authors.lastname: Noh
authors.forename: Janet
authors.initials: J
authors.lastname: Chen
authors.forename: Jin H
authors.initials: JH
authors.lastname: Kim
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: You