Potent Tumor-Specific Protection Ignited by Adoptively Transferred CD4+ T Cells

• Published in: The Journal of immunology (1950) 2008-09, Vol.181 (6), p.4363-4370
• Main Authors: Liu, Zuqiang, Noh, Hae S, Chen, Janet, Kim, Jin H, Falo, Louis D., Jr, You, Zhaoyang
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Cell Line, Tumor; Dose-Response Relationship, Immunologic; Female; Graft Rejection - immunology; Immunotherapy, Adoptive - methods; Interferon-gamma - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Mammary Neoplasms, Animal - immunology; Mammary Neoplasms, Animal - pathology; Mammary Neoplasms, Animal - therapy; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Neoplasm Invasiveness; Neoplasm Transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.6.4363

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.