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In vivo Expansion, Persistence, and Function of Peptide Vaccine–Induced CD8 T Cells Occur Independently of CD4 T Cells

Department of Immunology, Moffitt Cancer Center, Tampa, Florida

Requests for reprints: Esteban Celis, Moffitt Cancer Center, 12902 Magnolia Drive, SRB2, Tampa, FL 33612. Phone: 813-745-1925; Fax: 813-979-7265; E-mail: ecelis{at}moffitt.org.

Key Words: immunotherapy • peptide vaccines • T lymphocytes

Significant efforts are being devoted toward the development of effective therapeutic vaccines against cancer. Specifically, well-characterized subunit vaccines, which are designed to generate antitumor cytotoxic CD8 T-cell responses. Because CD4 T cells participate at various stages of CD8 T-cell responses, it is important to study the role of CD4 T cells in the induction and persistence of antitumor CD8 T-cell responses by these vaccines. Recent evidence points to the requirement of CD4 T cells for the long-term persistence of memory CD8 T cells, which in the case of cancer immunotherapy would be critical for the prevention of tumor recurrences. The purpose of the present study was to assess whether CD4 T cells are necessary for the generation and maintenance of antigen-specific CD8 T cells induced by subunit (peptide or DNA) vaccines. We have used a vaccination strategy that combines synthetic peptides representing CD8 T-cell epitopes, a costimulatory anti-CD40 antibody and a Toll-like receptor agonist (TriVax) to generate large numbers of antigen-specific CD8 T-cell responses. Our results show that the rate of decline (clonal contraction) of the antigen-specific CD8 T cells and their functional state is not affected by the presence or absence of CD4 T cells throughout the immune response generated by TriVax. We believe that these results bear importance for the design of effective vaccination strategies against cancer. [Cancer Res 2008;68(23):9892–9]