PREVENTION OF GRAFT-VERSUS-HOST DISEASE IN DLA-HAPLOTYPE MISMATCHED DOGS AND HEMATOPOIETIC ENGRAFTMENT OF CD6-DEPLETED MARROW WITH AND WITHOUT CG-CSF TREATMENT AFTER TRANSPLANTATION

Prevention of graft-versus-host disease by depletion of CD6-positive T cells as studied in the dog. Donors were DLA-homozygous, recipients D LA-heterozygous with one DLA haplotype identical to the donor. Seven c ontrol dogs received untreated marrow and died of GvHD after full hemo poietic recovery within 28 days of transplantation. For prevention of GVHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells completel y, but only part of CD8-positive cells and DR-positive cells. CD6-depl eted marrow exhibited strong nonspecific ''natural'' suppression of th e generation of cytotoxic T cells in vitro. Eleven dogs received CD6-d epleted marrow. Only 1 dog developed GvHD and died. Sustained engraftm ent was seen in 8 dogs. Hemopoietic recovery was delayed and slower af ter transplantation of CD6-depleted marrow than after transplantation of untreated marrow. Four of these dogs w ere treated with G-CSF and t his accelerated the recovery of leukocytes, but did not prevent reject ion. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prev ents GVHD across a DLA-haplotype difference, but rejection and mixed c himerism may occur. Treatment with G-CSF accelerates leukocyte recover y, but cannot prevent rejection.