INDUCTION OF GRAFT-VERSUS-HOST DISEASE IN SCID MICE BY MRL LPR CELL TRANSFER/

We have investigated the graft versus host (GvH) disease induced in im munodeficient SCID (H-2(d)) mice by intravenous (iv) or intraperitonea l (ip) transfer of either spleen or lymph node cells from autoimmune ( MRL/lpr and MRL/++ mice, H-2(k)) and normal (CBA, H-2(k)) mice. Rapid and lethal GvH disease was observed when cells from MRL/lpr or MRL/+were iv transferred into SCID mice, while spleen cells from nonautoimm une CBA donors were partially tolerized into SCID recipients and induc ed only lower levels of GVH reaction. No GvH reaction (complete tolera nce) was observed when CBA lymph node cells were iv transferred into S CID recipients. In contrast, the ip injection of MRL/lpr or CBA spleen cells induces similar levels of GvH. The development of GvH disease i n SCID recipients was due to the expansion of alloreactive CD8(+) cell s displaying significant cytotoxic activity against H-2(d), but not ag ainst autologous targets. Also, a significant decrease of CD4/CD8 rati o was observed in the course of GvH caused by the iv transfer of cells from MRL/lpr mice. Altogether, these data support the hypothesis that lymphocytes from the MRL/lpr mice may escape tolerance in the GvH rea ction. (C) 1994 Academic Press, Inc.