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International Immunology Advance Access originally published online on December 22, 2005
International Immunology 2006 18(2):325-333; doi:10.1093/intimm/dxh371
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells

Lara Myers1, Seung Woo Lee2, Robert J. Rossi1, Leo Lefrancois1, Byoung S. Kwon3, Robert S. Mittler4, Michael Croft2 and Anthony T. Vella1

1 Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
2 Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, La Jolla, CA 92121, USA
3 Immunomodulation Research Center, University of Ulsan, Ulsan, Republic of Korea
4 Department of Surgery and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA

Correspondence to: A. T. Vella; E-mail: vella{at}uchc.edu

In practice, vaccines should induce lasting and efficacious T cell immunity without promoting deleterious pathological consequences. To accomplish this goal we immunized mice with ovalbumin peptide, polyinosinic–polycytidylic and anti-CD137. Vaccinated mice retained a massive functional CD8 T cell memory pool in lymphoid and non-lymphoid tissues for >1 year. The memory T cells clonally expanded, produced substantial amounts of IFN{gamma}, and responded vigorously to vesicular stomatitis virus infection. To understand how the vaccine might function, we showed that the antigen-specific T cells must bear CD137 in order for optimal priming to occur. Thus, anti-CD137 agonist mAb directly stimulated peptide-specific CD8 T cells and conditioned them to survive. In contrast, CD137-deficient CD8 T cells did not survive despite CD137 expression by antigen presenting cells. Taken together, the data indicate that CD137 and adjuvant combined therapy is an efficacious vaccine strategy for immunization with non-replicating inert antigen.

Keywords: CD137, memory and adjuvant

Transmitting editor: P. Ohashi


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