OFFICE OF NAVAL RESEARCH CONTRACT N00014-88-C-0118 TECHNICAL REPORT 94-03 IMMUNE RESPONSES TO MHC HOMOZYGOUS LYMPHOID CELLS IN MURINE Fl HYBRID RECIPIENTS: IMPLICATIONS FOR TRANSFUSION ASSOCIATED GRAFT-VERSUS HOST DISEASE

Graft-versus-host disease(GVHD) is currently encountered following bone marrow transplantation and transfusion. GVHD associated with transfusion(TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the the recipient's HLA haplotypes. However the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model where GVHD is induced by the injection of parental lymphoid cells into unirradiated Fi hybrid recipients. The effect of various immune manipulations of the recipient on GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. While depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer(NK) cells in the downregulation of TA-GVHD development in recipients who receive blood from a haploidentical donor.