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

Human peripheral blood leucocytes (PBL) induce chronic graft versus-ho st disease (GvHD) in non-conditioned severe combined immunodeficient m ice. Chronic GvHD was observed in such animals after transplantation o f 6 x 10(7) human PBL per g body weight. However, acute xenogeneic GvH D 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 w ere thought to be required to produce above threshold amounts of certa in cytokines. We show that treatment of the recipient mice with human interleukin 2 reduces the number of cells to inflict acute GvHD by a f actor of ten. Human T cells and not B cells or macrophages, were previ ously shown to generate acute xenogeneic GvHD, when selected cell type s from peripheral blood were grafted. Most of the infiltrating cells h ad the CD4(+) phenotype. We demonstrate that CD4(+) T cells are the ma in mediator, as the disease is abrogated by treating the mice with cyt otoxic CD4 antibodies, but not with CD8 antibodies. A survival pattern , similar to that seen in GvHD, was induced by transplantation of a He rpesvirus saimiri transformed human CD4(+) clonal T cell line in conju nction with daily interleukin 2 injections. Herpesvirus saimiri transf ormed human T cells allow easily reproducible graft properties in chim eric mouse models for human diseases.