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Potent Tumor-Specific Protection Ignited by Adoptively Transferred CD4⁺ T Cells¹

Zuqiang Liu^*, Hae S. Noh^*, Janet Chen^*, Jin H. Kim^*, Louis D. Falo, Jr.^*, and Zhaoyang You^2,*,,

Departments of ^* Dermatology and Immunology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213

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- 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--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-^–/– 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a start-up fund from Department of Dermatology of University of Pittsburgh (to Z.Y.) and by National Institutes of Health Grants R01CA108813 (to Z.Y.) and R01CA106662 and P01CA73743 (to L.D.F.).

² Address correspondence and reprint requests to Dr. Zhaoyang You, W1046 Biomedical Sciences Tower, 200 Lothrop Street, Pittsburgh, PA 15213. E-mail address: youz{at}upmc.edu

³ Abbreviations used in this paper: Treg, CD4⁺CD25⁺ regulatory T cell; DC, dendritic cell; DT, diphtheria toxin; DTR, DT receptor; WT, wild type.

This article has been cited by other articles:

				Z. Liu, J. H. Kim, L. D. Falo Jr., and Z. You Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity J. Immunol., May 15, 2009; 182(10): 6160 - 6167. [Abstract] [Full Text] [PDF]

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