IL-12 administration leads to a transient depletion of T cells, B cells, and APCs and concomitant abrogation of the HLA-A2.1-restricted CTL response in transgenic mice

J Immunol. 2002 Jul 1;169(1):63-7. doi: 10.4049/jimmunol.169.1.63.

Abstract

The injection of a mixture of bona fide T cell epitopes can lead to the occurrence of immunodominance, meaning that the immune response is focused on the recognition of a single epitope or a small portion of the epitopes injected. We have previously demonstrated that the administration of rIL-12 can counteract immunodominance in BALB/c mice. In this study, we show that the administration of rIL-12 to HLA-A2.1 transgenic mice (A2k(b) mice) abrogates specifically the immune response against HLA-A2.1-restricted HIV epitopes in the spleen. This lack of immune response is most probably due to a transient depletion of B cells, T cells, macrophages, and dendritic cells in this organ. Therefore, our study explains the mechanism of immunosuppression by rIL-12 in vivo.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology
  • Animals
  • Antigen-Presenting Cells / immunology*
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic / genetics*
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • H-2 Antigens / genetics
  • HLA-A2 Antigen / biosynthesis
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology
  • Injections, Intraperitoneal
  • Interleukin-12 / administration & dosage*
  • Lymphocyte Depletion / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligopeptides / administration & dosage
  • Oligopeptides / immunology
  • Recombinant Proteins / administration & dosage
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes / immunology*

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • HLA-A2 Antigen
  • Immunodominant Epitopes
  • Oligopeptides
  • Recombinant Proteins
  • Interleukin-12