A tumor-associated and self antigen peptide presented by dendritic cells may induce T cell anergy in vivo, but IL-12 can prevent or revert the anergic state

J Immunol. 1997 Apr 15;158(8):3593-602.

Abstract

Ag-specific CD8+ cell responses, including delayed-type hypersensitivity in vivo and IFN-gamma production in vitro, are initiated by host immunization with P815AB, a self peptide bearing CTL epitopes and expressed by murine mastocytoma cells. Using P815AB-pulsed dendritic cells (DC) and monitoring class I-restricted skin test reactivity in DC-primed mice, we have previously shown that the development of a Th1-like response to P815AB requires T helper effects, such as those mediated by coimmunization with class II-restricted (helper) peptides or by the use of rIL-12. The adjuvanticity of IL-12 was suggested to involve improved recognition of class II-restricted epitopes of P815AB. In the present study, we provide evidence for the occurrence of I-A(d)-restricted epitopes in the tumor peptide. We also show that in the absence of helper peptide or rIL-12, P81 5AB not only failed to initiate CD8+ cell responses in vivo and in vitro, but resulted in a transient state of functional unresponsiveness, characterized by a profound inability of CD4+ cells to produce IL-2 in vitro. Ag-specific T cell anergy was also observed after neutralization of endogenous IL-12 at the time of priming with P815AB plus helper peptide. All of these effects were reversed by rIL-12, which was added to DC cultures and administered to the DC-recipient mice. Anergy induction may thus contribute to P81 5AB unresponsiveness in vivo. IL-12 may act to prevent or revert anergy to this tumor-associated and self peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Interleukin-12 / immunology*
  • Interleukin-12 / pharmacology
  • Mice
  • Mice, Inbred DBA
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Recombinant Proteins
  • Interleukin-12