title: Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection.
abstract: The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificities other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: T M
authors.initials: TM
authors.lastname: Coffman
authors.forename: D N
authors.initials: DN
authors.lastname: Howell
authors.forename: J
authors.initials: J
authors.lastname: Straznickas
authors.forename: M W
authors.initials: MW
authors.lastname: Scroggs
authors.forename: W M
authors.initials: WM
authors.lastname: Baldwin
authors.forename: P E
authors.initials: PE
authors.lastname: Klotman
authors.forename: F
authors.initials: F
authors.lastname: Sanfilippo
mesh_terms: D000818:Animals; D001803:Blood Transfusion; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection; D007249:Inflammation; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D016030:Kidney Transplantation; D008297:Male; D011300:Preoperative Care; D051381:Rats; D011912:Rats, Inbred ACI / Q000276:immunology; D011919:Rats, Inbred Strains / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013929:Thromboxane B2 / Q000096:biosynthesis; D014184:Transplantation, Homologous
chemical_list: D013929:Thromboxane B2