Kinetics of interferon‐γ secretion and its regulatory factors in the early phase of acute graft‐versus‐host disease

• Published in: Immunology Vol. 98; no. 3; pp. 379 - 385
• Main Authors: Hu, H. Z., Li, G. L., Lim, Y. K., Chan, S. H., Yap, E. H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.1999; Blackwell Science Inc
• Subjects: Acute Disease; Animals; Flow Cytometry; g-Interferon; Graft vs Host Disease - immunology; Interferon-gamma - blood; Interferon-gamma - metabolism; Interleukin-12 - immunology; Interleukin-18 - blood; Interleukin-18 - metabolism; Linear Models; Lymphocyte Activation; Mice; Mice, SCID; Original; Receptors, Interleukin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Statistics, Nonparametric; T-Lymphocytes - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.1999.00881.x

Summary Increased serum levels of interferon‐γ (IFN‐γ) have been observed in acute graft‐versus‐host disease (GVHD). Recent in vitro studies have demonstrated that interleukin‐12 (IL‐12) and interleukin‐18 (IL‐18) synergistically up‐regulate IFN‐γ secretion. In this communication, we investigated the factors relevant to IFN‐γ secretion in acute GVHD. A murine model of acute GVHD was established by injecting donor spleen cells into severe combined immunodeficiency (SCID) mice. A series of specimens, including sera, livers and spleens derived from the GVHD mice, were investigated with histological examination, enzyme‐linked immunosorbent assay (ELISA), flow cytometry, and semiquantitative reverse transcription–polymerase chain reaction (RT–PCR). IFN‐γ secretion increased in serum 3 days after spleen cell transfer, peaked on day 7, and then gradually decreased close to the baseline level by day 35. A synchronized increase of activated T cells and mRNA expression of IL‐12, IL‐18 and their respective receptors was observed after spleen cell transfer. However, only the kinetic expression pattern of IL‐12 receptor (IL‐12R) β2 chains was closely correlated with that of IFN‐γ, while IL‐12 dropped to the baseline level earlier than IFN‐γ. Therefore, IFN‐γ expression in the early phase of acute GVHD is a mono‐peak and self‐restricted pattern. Its secretion is closely related with T‐cell activation, the presence of IL‐12, IL‐18 and their respective receptors. However, the limiting factors for IFN‐γ secretion seem to be IL‐12 and IL‐12R β2 chains.