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IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8⁺ T Cell Responses and Increases the Ratio of Effector/Memory CD8⁺ T Cells to Regulatory T Cells¹

Sven Mostböck^*, M. E. Christine Lutsiak^*, Diane E. Milenic, Kwamena Baidoo, Jeffrey Schlom^2,* and Helen Sabzevari^*

^* Laboratory of Tumor Immunology and Biology, Center for Cancer Research and Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4⁺ and CD8⁺ T cell activation/expansion and as an essential cytokine for the maintenance of CD4⁺CD25⁺FoxP3⁺ T cells (regulatory T (T_REG) cells) during homeostasis. In this study we demonstrate for the first time that, compared with the use of IL-2 alone, a complex of IL-2 and anti-IL-2 Ab (IL-2 complex) enhances the effectiveness of a viral vaccine in a mouse model with known Ag specificity. IL-2 complex led to an increase in the number of Ag-specific effector/memory CD8⁺ T cells, cytokine production, and CTL lysis following Ag-specific restimulation in a vaccination setting. Our results further demonstrate that this effect is temporary and declines over the course of a few days after the IL-2 complex treatment cycle. Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8⁺ T cells to T_REG cells. This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination.

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 research was supported by the Intramural Research Program of National Institutes of Health, National Cancer Institute, Center for Cancer Research.

² Address correspondence and reprint requests to Dr. Jeffrey Schlom, Building 10 Room 8B09, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892. E-mail address: js141c{at}nih.gov

³ Abbreviations used in this paper: T_REG, regulatory T (CD4⁺CD25⁺FoxP3⁺) cell; CHX-A''-DTPA, isomer of 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriaminepentaacetic acid; IL-2 complex, complex of IL-2 and anti-IL-2 Ab; NK cell, CD3e^–NK1.1⁺DX5⁺; NP, nucleoprotein; NP68, influenza NP₃₆₆-₃₇₄ sequence ASNENMDAM; rV-NP-GFP/TRICOM, recombinant vaccinia vector expressing a fusion protein of influenza NP, enhanced GFP, and TRICOM; rF-GM-CSF, recombinant fowlpox vector expressing GM-CSF; TRICOM, triad of costimulatory molecules B7.1, LFA-3, and ICAM-1.

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