Differential Effects of IL-12 on the Generation of Alloreactive CTL Mediated by Murine and Human Dendritic Cells: A Critical Role for Nitric Oxide

J Leukoc Biol. 2003 May;73(5):621-9. doi: 10.1189/jlb.0402205.

Abstract

We examined the mechanisms involved in interleukin (IL)-12-mediated suppression of cellular immunity in mice using allogeneic mixed leukocyte reaction (MLR) stimulated by dendritic cells (DCs) in vitro and compared the effect of IL-12 on MLR in mice and humans. Although IL-12 stimulated human MLR, the addition of IL-12 or interferon-gamma (IFN-gamma) resulted in a dose-dependent suppression of MLR in mice. The treatment with N(G)-monomethyl-L-arginine (L-NMMA) completely abrogated IL-12- and IFN-gamma-mediated suppression of MLR in mice. Furthermore, IL-12 enhanced the alloreactive cytolytic T lymphocyte (CTL) induction in human MLR, whereas the addition of L-NMMA was required to generate alloreactive CTLs in the presence of IL-12 in mice. Nitric oxide (NO) was detected only in mouse MLR. Murine DCs could produce NO, but neither human CD34(+) cell- nor monocyte-derived DCs produced a detectable amount of NO. These results suggest that NO produced by DCs might play an important role in IL-12-mediated immune suppression in mice but not in humans.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Humans
  • Immune Tolerance / physiology
  • Immunity, Cellular / drug effects
  • Interferon-gamma / pharmacology
  • Interleukin-12 / pharmacology*
  • Lymphocyte Culture Test, Mixed
  • Lymphoma, T-Cell / pathology
  • Mastocytoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Species Specificity
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • omega-N-Methylarginine / pharmacology

Substances

  • Nitric Oxide Donors
  • Interleukin-12
  • omega-N-Methylarginine
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Interferon-gamma