CD4+CD25+ regulatory T cells that secrete TGFbeta and IL-10 are preferentially induced by a vaccine vector

J Immunother. Sep-Oct 2004;27(5):339-46. doi: 10.1097/00002371-200409000-00002.

Abstract

CD4CD25 T cells generated in a vaccine scenario can play a critical role in limiting antitumor therapy, thus having widespread implications for the immunotherapy-based treatment of cancer. The authors previously used Listeria monocytogenes to develop two vaccine constructs that express HPV-16 E7 protein and induce strong cellular immunity to HPV-E7-expressing tumors. Immunization of mice bearing established E7-expressing tumors with Lm-LLO-E7 induced regression of the tumors, whereas Lm-E7 showed little or no tumor regression. To investigate the possibility that regulatory CD4CD25 T-cell populations may be responsible for the differences in tumor regression, the authors characterized the role of these cells generated by the two vaccine systems. The authors compared the prevalence of CD4CD25 T cells in tumor-bearing vaccinated mice and demonstrate that Lm-E7-vaccinated mice have significantly increased numbers of CD4CD25 T cells in both the spleen and tumor-infiltrating lymphocytes compared with Lm-LLO-E7-vaccinated mice. The authors confirm that these increased numbers of CD4CD25 T cells are indeed suppressor in function by in vitro suppression assays and that the mechanism of action of the tumor-infiltrating cells involves the production of suppressor cytokines interleukin-10 and transforming growth factor beta. These results show that it is possible for a tumor vaccine system to generate tumor-infiltrating CD4CD25 regulatory T cells that critically affect tumor regression and the overall success of vaccine therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Toxins / immunology
  • Bacterial Vaccines / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Flow Cytometry
  • Genetic Vectors
  • Heat-Shock Proteins / immunology
  • Hemolysin Proteins
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / immunology
  • Listeria monocytogenes
  • Mice
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus E7 Proteins
  • Receptors, Interleukin-2 / immunology*
  • Recombinant Proteins / immunology
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / immunology

Substances

  • Bacterial Toxins
  • Bacterial Vaccines
  • Cancer Vaccines
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • oncogene protein E7, Human papillomavirus type 16
  • Interleukin-10
  • hlyA protein, Listeria monocytogenes