CYTOKINE DEPENDENCE OF HUMAN TO MOUSE GRAFT-VERSUS-HOST DISEASE

Human peripheral blood leucocytes (PBL) induce chronic graft versus-host disease (GvHD) in non-conditioned severe combined immunodeficient mice. Chronic GvHD was observed in such animals after transplantation of 6 x 10(7) human PBL per g body weight. However, acute xenogeneic GvHD results from grafting at least 2 x 10(7) human PBL per g body weight to heavily conditioned murine hosts. The large numbers of human PBL were thought to be required to produce above threshold amounts of certain cytokines. We show that treatment of the recipient mice with human interleukin 2 reduces the number of cells to inflict acute GvHD by a factor of ten. Human T cells and not B cells or macrophages, were previously shown to generate acute xenogeneic GvHD, when selected cell types from peripheral blood were grafted. Most of the infiltrating cells had the CD4(+) phenotype. We demonstrate that CD4(+) T cells are the main mediator, as the disease is abrogated by treating the mice with cytotoxic CD4 antibodies, but not with CD8 antibodies. A survival pattern, similar to that seen in GvHD, was induced by transplantation of a Herpesvirus saimiri transformed human CD4(+) clonal T cell line in conjunction with daily interleukin 2 injections. Herpesvirus saimiri transformed human T cells allow easily reproducible graft properties in chimeric mouse models for human diseases.