Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells: a critical role for nitric oxide

• Published in: Journal of leukocyte biology Vol. 73; no. 5; pp. 621 - 629
• Main Authors: Nishioka, Yasuhiko, Wen, Hua, Mitani, Kayo, Robbins, Paul D., Lotze, Michael T., Sone, Saburo, Tahara, Hideaki
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-05-2003
• Subjects: Animals; Antigen Presentation; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Humans; IFN‐γ; Immune Tolerance - physiology; Immunity, Cellular - drug effects; Interferon-gamma - pharmacology; Interleukin-12 - pharmacology; Lymphocyte Culture Test, Mixed; Lymphoma, T-Cell - pathology; L‐NMMA; Mastocytoma - pathology; Mice; Mice, Inbred C57BL; MLR; Nitric Oxide - biosynthesis; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; omega-N-Methylarginine - pharmacology; S-Nitroso-N-Acetylpenicillamine - pharmacology; Species Specificity; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0402205

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‐γ (IFN‐γ) resulted in a dose‐dependent suppression of MLR in mice. The treatment with NG‐monomethyl‐l‐arginine (L‐NMMA) completely abrogated IL‐12‐ and IFN‐γ‐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.