Interleukin-6 in islet xenograft rejection.
Earlier work on primate cardiac xenotransplantation has demonstrated a correlation between interleukin (IL)-6 levels and severity of vascular rejection. IL-6 was originally identified as a lymphokine inducing final maturation of B lymphocytes into antibody-secreting cells. The present study aimed to evaluate the role of IL-6 in fetal porcine islet-like cell cluster (ICC) xenograft rejection. Moreover, other authors have reported that eosinophils dominate the cellular response following discordant islet xenograft transplantation. Here, a technique for specific detection of eosinophils was applied. IL-6-deficient mice and wild-type controls were implanted with fetal porcine ICCs under the kidney capsule and killed 4-, 7-, and 10 days after transplantation. Xenografts were histologically evaluated, and serum samples were analyzed for IgM and IgG antibodies against ICC membrane antigens. IL-6-deficient mice and wild-type controls readily rejected the xenograft. On day 7 after transplantation, abundant numbers of F4/80+ and Mac-1+ cells were found distributed throughout the collapsing graft accompanied by small amounts of eosinophils and peripherally accumulated CD3+ T cells (predominantly CD4+). Significantly lower serum levels of IgM and IgG antibodies against ICC membrane antigens were observed in IL-6-deficient mice on day 4 or 7 after transplantation when compared to wild-type controls. No significant differences were seen on day 10 after transplantation. In both experimental groups, specific IgM and IgG antibody levels remained stable over time. In the pig-to-mouse model, IL-6 seems to be of minor importance to fetal porcine ICC xenograft rejection. Macrophages, and not eosinophils, dominate the cellular response associated with this process.
Benda
B
B
Section of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, The Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden.
Korsgren
O
O
D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013552:Swine; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D015850:Interleukin-6