Enhanced interferon-alpha/beta (IFN-alpha/beta) and defective IFN-gamma production in chronic graft versus host disease: a potential mechanism for immunosuppression.
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.
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002908:Chronic Disease; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D007108:Immune Tolerance; D007370:Interferon Type I / Q000096:biosynthesis* / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D013154:Spleen / Q000378:metabolism / Q000637:transplantation
D007370:Interferon Type I; D007376:Interleukin-2; D003208:Concanavalin A; D007371:Interferon-gamma