ARTÍCULO

A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice

Autores: Casares Lagar, Noelia; Rudilla Salvador, Francesc; Arribillaga Arangoa, Laura; Llopiz Khatchikian, Diana Isabel; Riezu Boj, José Ignacio; Lozano Moreda, Teresa; López Sagaseta, Jacinto; Guembe Echarri, Laura; Sarobe Ugarriza, Pablo; Prieto Valtueña, Jesús María; Borras Cuesta, Francisco; Lasarte Sagastibelza, Juan José
Título de la revista: JOURNAL OF IMMUNOLOGY
ISSN: 0022-1767
Volumen: 185
Número: 9
Páginas: 5150 - 5159
Fecha de publicación: 2010
Resumen:
Immunosuppressive activity of regulatory T cells (Treg) may contribute to the progression of cancer or infectious diseases by preventing the induction of specific immune responses. Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg. P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-¿B and NFAT. In vitro, P60 inhibited murine and human-derived Treg and improved effector T cell stimulation. P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3. However, P60 did not cause toxic effects in adult mice and, when given to BALB/c mice immunized with the cytotoxic T cell epitope AH1 from CT26 tumor cells, it induced protection against tumor implantation. Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus. Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.