Enhanced interferon-α/β (IFN-α/β) and defective IFN-γ production in chronic graft versus host disease: a potential mechanism for immunosuppression

• Published in: Cellular immunology Vol. 110; no. 1; pp. 120 - 130
• Main Authors: CLEVELAND, M. G, LANE, R. G, KLIMPEL, G. R
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 01.11.1987
• Subjects: Acute Disease; Animals; Applied sciences; Bone Marrow Transplantation; Cells, Cultured; Chronic Disease; Concanavalin A - pharmacology; Exact sciences and technology; Female; Graft vs Host Disease - blood; Graft vs Host Disease - immunology; Immune Tolerance; Interferon Type I - biosynthesis; Interferon Type I - blood; Interferon-gamma - biosynthesis; Interferon-gamma - blood; Interleukin-2 - pharmacology; Lymphocyte Activation - drug effects; Mice; Mice, Inbred Strains - immunology; Other techniques and industries; Spleen - metabolism; Spleen - transplantation
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/0008-8749(87)90106-7

Immunosuppression is a well-characterized consequence of chronic graft-versus-host disease (GVHD). We have previously shown that interferon (IFN) is produced in high levels during acute GVHD. Our objective in this study was to determine if IFN, as a cytokine with known immunosuppressive qualities, could be detected in mice experiencing chronic GVHD-induced immunosuppression. Two different experimental models were used to induce chronic GVHD. The first model involved the injection of parental strain spleen cells into adult F1 hybrids (AJ---B6AF1), while the second model utilized GVHD induced across minor histocompatibility barriers (B10.D2---BALB/c). Results indicated that significant levels of serum IFN-alpha/beta are present in mice undergoing chronic GVHD. Spleen cells from chronic GVHD mice were also shown to produce significant levels of IFN-alpha/beta upon in vitro culture in medium only. This IFN-alpha/beta production was greatly increased when GVHD spleen cells were cultured with either concanavalin A (Con A) or IL-2. In contrast, IFN-gamma production was undetectable in these Con A- or IL-2-containing cultures. Additionally, these same spleen cells which produced high levels of IFN-alpha/beta were immunosuppressed as measured by mitogen-induced cell proliferation. These results suggest that IFN-gamma production is defective in GVHD spleen cells, and that the presence of high IFN-alpha/beta production by GVHD mice may contribute to the immunosuppression associated with chronic GVHD.