A ROLE FOR TH2 CYTOKINES IN THE SUPPRESSION OF CD8(-CELL-MEDIATED GRAFT-REJECTION() T)

A major histocompatibility complex (MHC) class I-specific T cell recep tor (TCR)-transgenic mouse was used to study classical-type transplant ation tolerance in the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to donor-type skin grafts were obtained usin g dimethylmyeleran (DMM) as a myeloablative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the sole immunosuppressant. Surp risingly, bone marrow engraftment was facilitated by host CD4(+) T cel ls, a subset normally considered unable to reject class I MHC-incompat ible grafts. A combination of mAb to interleukins (IL)-4 and -10 antag onized the ''permissive'' effects of host CD4(+) T cells, indicating a possible role for Th2-type immunoregulation that can act on CD8(+) T cells in this form of transplantation tolerance. The fate of graft-rea ctive T cells was monitored using anti-clonotypic antibodies. It was o bserved that bone marrow engraftment then led to peripheral deletion o f mAb-blockaded, clonotype(+) CD8(+) T cells.