title: Cardia allograft unresponsiveness using a posttransplant strategy : characterization of the graft infiltrate.
abstract: We evaluated a combined posttransplant strategy using antilymphocyte serum (ALS) at time of engraftment followed by low dose total lymphoid irradiation (TLI) and donor bone marrow cell (BMC) inoculation administered either intrathymically (IT) or intravenously (IV) in the vigorously rejecting strain combination DA into Lew recipients. Allograft survival was significantly prolonged with administration of ALS in combination with TLI and IT (105 +/- 28.6 days) or IV (106.8 +/- 28.6 days) BMC compared to administration of ALS combined with either TLI (17.8 +/- 0.4 days) or BMC (9.0 +/- 0.0 days), or TLI combined with BMC (1 1.5 +/- 0.5 days) (P < 0.000 1, experimental vs control animals). There was no difference in survival between those animals who underwent IT or IV BMC inoculation. Third-party (WF) BMC inoculation did not significantly prolong allograft survival (10.0 +/- 1.0 days). A mild to moderate cellular infiltrate was present in allograft tissue after 100 days. To further characterize these cells, cytokine mRNA expression in allograft tissue (> 100 days posttransplant) was evaluated using nonisotopic in situ hybridization. A similar cytokine profile was demonstrated in allograft tissue compared to naive and isograft tissue, except for a slight increase in IL-2 (P < 0.02, control vs IV BMC; P = NS, other groups). In summary, unresponsiveness was induced in a high-responder strain combination using a combined posttransplant strategy of ALS, TLI, and donor antigen either IT or IV. The cytokine profile of the graft infiltrating cells was similar to that of normal tissue. Unresponsiveness may be the result of functional inactivation of these cells.
authors.affiliation: Department of Surgery, Stanford University, California 94305, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Krieger
authors.forename: V R
authors.initials: VR
authors.lastname: Quezada
authors.forename: P
authors.initials: P
authors.lastname: Huie
authors.forename: B
authors.initials: B
authors.lastname: Holm
authors.forename: R K
authors.initials: RK
authors.lastname: Sibley
authors.forename: D C
authors.initials: DC
authors.lastname: Dafoe
authors.forename: E J
authors.initials: EJ
authors.lastname: Alfrey
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002678:Chimera; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D013997:Time Factors; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D000961:Antilymphocyte Serum; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma