Dendritic cells, interleukin 12, and CD4+ lymphocytes in the initiation of class I-restricted reactivity to a tumor/self peptide

Crit Rev Immunol. 1998;18(1-2):87-98. doi: 10.1615/critrevimmunol.v18.i1-2.100.

Abstract

Cell-mediated immunity involving CD8+ lymphocytes is effective in mediating rejection of murine mastocytoma cells bearing P815AB, a tumor-associated and self antigen showing similarity to tumor-specific shared antigens in humans. Although this antigen may act as an efficient target for class I-restricted responses in immunized mice, neither P815AB expressed on tumor cells nor a related synthetic nonapeptide will activate unprimed CD8+ cells for in vivo reactivity, measured by skin test assay. We review evidence showing that the failure of P815AB to initiate CD8+ cell reactivity may be due to defective recruitment of accessory and Th1-like cells to the afferent phase of the response initiated by transfer of mice with dendritic cells pulsed in vitro with the P815AB peptide. Although the copresence of a T helper peptide in dendritic cell priming in vitro with P815AB may compensate for the poor generation of accessory and Th1 cells in the adoptively transferred mice, recombinant IL-12 can replace the helper peptide in both effects. Effective priming to P815AB in vivo is achieved by either exposing dendritic cells to IL-12 prior to P815AB priming or administering the recombinant cytokine in vivo. Different approaches suggest that IL-12 may act both on accessory cells to improve presentation of previously undescribed class II-restricted epitopes of P815AB and on CD4+ cells to improve recognition of such epitopes. In particular, at the CD4+ cell level, IL-12 apparently acts as an adjuvant and an inhibitor of anergy induction. These data offer useful information for developing vaccination strategies using dendritic cells and class I-restricted tumor peptides in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Clonal Anergy
  • Dendritic Cells / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Interleukin-12 / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • Recombinant Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptides
  • Recombinant Proteins
  • tumor rejection antigen P815A, mouse
  • Interleukin-12