Specific suppressor cells and immune response to host antigens in long-term human allogeneic marrow recipients: implications for the mechanisms of graft-host tolerance and chronic graft-versus-host disease.

After marrow grafting from HLA-identical siblings, anti-host immune reactivity and suppressor activity were examined in long-term patients with and without C-GVHD. Lymphocytes (of donor origin) from 17 of 32 patients with C-GVHD showed MLR to non-HLA antigens of stored host lymphocytes, and lymphocytes from 8 of 21 patients with C-GVHD exhibited cytotoxicity to host skin fibroblasts. Lymphocytes from only 2 of 15 patients without C-GVHD, however, showed significant MLR to host lymphocytes and none of 16 had cytotoxicity to host fibroblasts. Suppressor activities differed in the two patient groups. Patients without C-GVHD had circulating suppressor cells that specifically inhibited donor MLR to TNP-host lymphocytes but not to TNP-donor, TNP-unrelated and unmodified unrelated lymphocytes. On the other hand, patients with C-GVHD had predominantly suppressor cells that inhibited donor MLR to TNP-unrelated and unmodified unrelated lymphocytes. These findings indicate that anti-host immune reactivity in the absence of specific suppressor cells plays a role in C-GVHD, and that graft-host tolerance in the stable chimeras may be maintained by specific suppressor cells.