IL-7 adjuvant treatment enhances long-term tumor-antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector

Blood. 2009 Jun 25;113(26):6629-37. doi: 10.1182/blood-2008-05-155309. Epub 2009 Apr 21.

Abstract

Immunization with recombinant lentivector elicits higher frequencies of tumor antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding correlates with our observation that, upon recombinant lentivector immunization, a higher fraction of antigen-specific effector CD8+ T cells does not down-regulate the expression of the survival/memory marker interleukin-7 receptor alpha chain (IL-7Ralpha). Here we show that, surprisingly, higher expression of IL-7Ralpha on recombinant lentivector-induced effector CD8+ T cells does not result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiologic levels of IL-7 might be limiting in vivo for delivering survival signals to the expanding population of effector cells. To test this hypothesis, we administered recombinant IL-7 during the effector phase of the response. We observed an up-regulation of Bcl-2 and a strong expansion of antigen-specific effector CD8+ T cells, and of naive CD8+ T cells. Strikingly, IL-7 treatment elicited also a significant increase in the number of antigen-specific memory CD8+ T cells in recombinant lentivector-immunized mice, but not in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant treatment can enhance long-term antigen-specific CD8+ T-cell responses. However, its efficacy depends on the expression of IL-7Ralpha at the surface of effector CD8+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology*
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • Humans
  • Immunization
  • Immunologic Memory
  • Interferon-gamma / biosynthesis
  • Interleukin-7 / pharmacology*
  • Lentivirus / genetics
  • Lentivirus / immunology*
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Interleukin-7 / metabolism
  • Recombinant Proteins / pharmacology
  • Specific Pathogen-Free Organisms
  • T-Cell Antigen Receptor Specificity
  • Up-Regulation / drug effects
  • Vaccines, Subunit / immunology*

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • H-2 Antigens
  • H-2Kb protein, mouse
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • IL7 protein, human
  • Interleukin-7
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-7
  • Recombinant Proteins
  • Vaccines, Subunit
  • interleukin-7 receptor, alpha chain
  • Interferon-gamma