SPLIT TOLERANCE BETWEEN SPLEEN AND LYMPH-NODE CELLS IN SEVERE COMBINED IMMUNODEFICIENCY MICE GRAFTED WITH AKR FETAL LIVER-CELLS

Severe combined immunodeficient (SCID) mice defective in stem cells fo r T and B cells appear to be an ideal host for construction of chimeri c mice. When bone marrow cells are used as a source of stem cells, how ever, host SCID mice do not always show sufficient reconstitution. In this study, fetal liver cells from AKR embryos were transplanted into SCID mice without prior irradiation. This treatment induced full recon stitution of lymphopoiesis as evaluated by flow cytometry analysis and serum Ig production 2 months after transplantation. Thus, fetal liver cells seem to be a better source for reconstitution of SCID mice than bone marrow cells, Lymph node (LN) cells of these mice (FLT mice) had no proliferative or cytotoxic activities against either host-type (C. B-17) or donor-type (AKR) spleen cells. However, spleen cells from FLT mice exhibited marked proliferative and cytotoxic activities against C.B-17 cells, with no activities against AKR cells. Split tolerance ag ainst C.B-17 cells in spleen and LN cells was not a transient phenomen on, since similar results were obtained from a cytotoxic T lymphocyte assay 4 months later. In spite of the strong host reactivity in vitro, aberration of clonal deletion or development of a graft-versus-host d isease was not seen in FLT mice. As IL-2 induced the host reactivity o f LN cells in a mixed lymphocyte reaction, potentially host-reactive T cells were present in LN but were rendered anergic. Tolerance in FLT mice seems to be regulated by a peripheral mechanism. We supposed that the split tolerance in FLT mice was induced by the different antigeni city between the spleen and LN.