DONOR BLOOD MONOCYTES BUT NOT T-CELLS OR B-CELLS FACILITATE LONG-TERMALLOGRAFT SURVIVAL AFTER TOTAL LYMPHOID IRRADIATION

Background, Previous studies showed that a combination of posttranspla nt total lymphoid irradiation (TLI), rabbit antithymocyte globulin (AT G), and a single donor blood transfusion induced tolerance to ACI hear t allografts in Lewis rats. All three modalities were required to achi eve tolerance. The objective of the current study was to determine the subset(s) of cells in the donor blood that facilitated long-term allo graft survival. Methods. Lewis hosts received TLI, ATG, and donor cell infusion after heart transplantation, Graft survival, mixed leukocyte reaction (MLR), and intragraft cytokine mRNA were studied. Results. T he intravenous injection of 25 x 10(6) ACI peripheral blood mononuclea r cells (PBMC) significantly prolonged graft survival as compared with that of Lewis hosts given TLI and ATG alone. Injection of highly enri ched blood T cells or splenic B cells adjusted for the number containe d in 25 x 10(6) PBMC failed to induce significant graft prolongation, Unexpectedly, depletion of monocytes (CD11b(+) cells) from PBMC result ed in the loss of graft prolongation activity. Enriched populations of monocytes obtained by plastic adherence were more efficient in prolon ging graft survival than PBMC on a per cell basis, Hosts with long-ter m grafts (>100-day survival) showed evidence of immune deviation, beca use the MLR to ACI stimulator cells was vigorous, but secretion of int erferon-gamma in the MLR was markedly reduced. In situ hybridization s tudies of long-term grafts showed markedly reduced levels of interfero n-gamma mRNA as compared with rejecting grafts. Conclusion, Infusion o f donor monocytes facilitated graft prolongation via immune deviation.