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1.
《中华实验外科杂志》2009,26(10)
目的 探讨经门静脉途径输注供体骨髓细胞后,大鼠小肠移植中受体基因嵌合率的改变及可能机制.方法 建立大鼠异位节段小肠移植模型(供体为雄性BN,受体为雌性Lewis,各15只),并将其随机分为三组,对照组、FK506组、PV组(喂养FK506及经门静脉注射供体骨髓细胞组).应用原位荧光杂交定位检测以及实时定量聚合酶链反应技术分析供体雄性细胞的SRY基因在移植术后受体大鼠血液、肝脏及脾脏中的嵌合情况.结果 PV组受体雌性大鼠血液(3.03±0.16)%、肝脏(0.86±0.05)%、脾脏(4.08±0.12)%中供体SRY基因嵌合率均较FK506组(1.15±0.07)%、(0.21±0.02)%、(1.23±0.05)%、对照组(1.10±0.07)%、(0.22±0.02)%、(1.17±0.06)%明显增高(P<0.01).结论 经门静脉系统输注供体骨髓细胞可建立稳定的混和嵌合体状态. 相似文献
2.
Irmeli Lautenschlager Björn Nashan Hans-Jürgen Schlitt Burckhardt Ringe Kurt Wonigeit Rudolf Pichlmayr 《Transplant international》1995,8(6):446-451
In this retrospective study, we have investigated the early intragraft inflammatory events of 12 liver allografts leading to chronic rejection. The cytological findings and clinical follow-up were analyzed in detail. Nine patients underwent at least one typical lymphoid activation of acute rejection, and three of them were treated more than once. Diagnosis of rejection was based on biopsy histology, cytology and liver dysfunction. In addition to the acute rejections, cytological analysis demonstrated in 11 of 12 grafts an unidentified lymphoid episode that differed from that of rejection. These lymphoid responses were associated with viral infections; cytomegalovirus (CMV) infection in 10 of 12 patients, hepatitis C virus (HCV) infection in 2 of 12 patients, 1 combined with CMV, and hepatitis B virus (HBV) infection in 1 patient. Graft dysfunction was still seen at the end of the follow-up. Thus, intragraft inflammation caused either by acute rejection or by viral infections may be involved in the induction of chronic rejection. 相似文献
3.
Yoshinori Shimizu Shigeru Goto Roger Lord Frank Vari Catherine Edwards-Smith Satoshi Chiba D. Schlect M. Buckley Mitsuo Kusano Naoshi Kamada 《Transplant international》1996,9(6):593-595
The tolerance induced by orthotopic liver transplantation (OLT) in certain combinations of rat strains can be prevented by total body irradiation (TBI) of the donor. We demonstrate here that the intravenous inoculation of splenic leukocytes into irradiated donors before OLT could re-establish tolerance in association with a state of microchimerism detected in the recipients. When donor DA (RT1a) strain rats were irradiated with 1000 rad 24 h before liver harvesting and subsequent liver implantation into PVG recipients, five out of six rats died from rejection in this normally tolerogenic OLT (DA-PVG) combination. Injection of 1.5x108 splenic leukocytes from naive DA rats into the irradiated DA donor rats 24 h before OLT restored the tolerogenic potential of the liver allografts. Immunofluorescence assay revealed an increased number of donor (DA) type cells in the PVG recipient bearing a repopulated DA liver, compared to the PVG recipient of an irradiated liver. These results suggest that passenger leukocytes reconstituted by splenic leukocytes have the capacity to protect liver allografts. 相似文献
4.
Veronika Grau Gabriele Fuchs-Moll Gabriela Krasteva Markus Hirschburger Birte Steiniger Winfried Padberg 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2008,393(2):219-226
Background After transplantation, passenger leukocytes move to lymphoid organs of the recipient. These cells appear to initiate allograft
rejection, but they also might be involved in tolerance induction.
Materials and methods Orthotopic left lung transplantation was performed in the Dark Agouti to Lewis rat strain combination with no immunosuppression.
Recipient spleens were removed at intervals of 24 h until day 6 after transplantation. For comparison, spleens from renal
allograft recipients were analysed. Donor-derived major histocompatibility complex (MHC) class II antigens were detected by
monoclonal antibody OX76. In double-staining experiments with antibodies specific for leukocyte subpopulations, their localisation
and identity was analysed.
Results OX76-positive leukocytes were already detected in recipient spleens on day 1 post-transplantation. They increased in number
until day 3 and decreased in number thereafter. Most of them were localised in splenic follicles and expressed the B cell
variant of CD45R and IgG. Cell surface antigens typical for other leukocyte subpopulations were not detected. In the spleens
of renal allograft recipients, only few donor-derived cells were seen.
Conclusion After lung transplantation, numerous MHC class II-positive B cells migrate to the splenic follicles of the recipient. These
cells might, in part, be responsible for immunologic differences observed between renal and pulmonary allografts.
Best abstracts - Surgical Forum 2007 相似文献
5.
F. R. Pruvot F. Navarro A. Janin M. Labalette E. Masy M. Lecomte-Houcke L. Gambiez M. C. Copin J. P. Dessaint 《Transplant international》1995,8(4):273-279
Quantification and localization of the main lymphocyte populations were studied in the livers of normal (n=8) and brain dead (n=8) subjects. Cytometric analysis performed on mononuclear cell suspensions obtained from liver biopsies was compared to an automatic image analysis of immunostained sections. The overall number of liver associated lymphocytes was in the usual range of peripheral blood content (2 to 9 · 109 cells). Phenotypic analysis showed predominant NK and CD8+ cells that highly expressed class II antigen and CD25 and CD69 activation markers. Quantitative mapping of these activated lymphocytes revealed their preferential localization in the portal tract and the perisinusoidal area as compared to the pericentrolobular zone, especially in donor livers. This strategic localization could suggest a possible early cooperation between donor lymphocytes and initial infiltrating cells from the recipient and could explain the special immunological status of allografted livers. 相似文献
6.
O. Sanada Y. Fukuda R. Sumimoto S. Hoshino M. Nishihara K. Kaneda T. Asahara K. Dohi 《Transplant international》1998,11(S1):S174-S178
Abstract In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1–2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats. 相似文献
7.
8.
T. Matsuura Masaaki Imanishi Yasushi Hara Tsukasa Nishioka Seiji Kunikata Takahiro Akiyama Takashi Kurita 《Transplant international》1997,10(4):262-267
Intrathymic injection of donor bone marrow cells (ITBMCs) at the time of transplantation and treatment with antilymphocyte
serum (ALS) permitted the indefinite survival of Brown Norway (BN, RT1n) rat heart grafts in 6 out of 8 Lewis (LEW, RT1l) rat recipients. LEW recipients with long-surviving BN heart grafts (LSGs) also accepted additional BN heart grafts without
further immunosuppression, though they rejected Piebald Virol Glaxo (PVG, RT1c) rat heart grafts in the usual fashion. In the in vitro study, the proliferative response of the lymphocytes from LEW recipients
with LSGs remained suppressed when they were stimulated by BN spleen cells, but not when stimulated by PVG cells. Bone marrow
cells (BMCs) from LEW rats with LSGs showed strong, nonspecific, suppressive effects on the proliferative response in the
mixed lymphocyte culture reaction, suggesting that one of the possible explanations for tolerance might be the involvement
of a suppressor mechanism.
Received: 7 August 1996 Received after revision: 12 February 1997 Accepted: 17 February 1997 相似文献
9.
S. Chiba S. Goto Yoshinori Shimizu Frank Vari Roger Lord Catherine Edwards-Smith Shigeru Kobayashi Takenori Ochiai Kaichi Isono 《Transplant international》1997,10(5):350-356
The tolerance induced by orthotopic liver transplantation [DA (RT1a) rats to PVG (RT1c) rats] can be prevented by total body irradiation of the donor rat.
Reconstitution of the irradiated donor with DA splenic leukocytes reintroduces this tolerance. To investigate the major histocompatibility
complex (MHC) specificity of passenger leukocytes, irradiated DA donors were reconstituted by third-party BN (RT1n) splenic leukocytes. The reconstitution with BN splenocytes re-established DA-specific tolerance in PVG recipients, as confirmed
by subsequent DA cardiac allografting, while BN hearts were rejected with second-set tempo. To determine which cell components
play an important role in re-establishing liver graft tolerance, DA splenic leukocytes were further purified into three types:
T, B, and adherent cells. Only “T-cell-enriched” preparations restored liver graft tolerance in three out of five PVG recipients.
These results suggest that passenger leukocytes of differing MHC types can help to induce liver-specific tolerance and that
T cells in the liver graft may be essential to regulate tolerance induction.
Received: 31 December 1996 Received after revision: 14 April 1997 Accepted: 15 April 1997 相似文献
10.
目的探讨负载供肾抗原的致耐受性受者树突状细胞(DCs)对移植肾存活时间的影响。方法以BN大鼠为供者,Lewis大鼠为受者,Wistar大鼠为无关供者。将受者的骨髓分离培养,未经其它处理得到的DCs,将其作为DCs1;DCs1经CTLA-4Ig基因重组的复制缺陷型腺病毒(AdvCTLA-4Ig)转染后作为DCs2;DCs1先经BN大鼠供肾抗原负载后再进行AdvCTLA-4Ig转染,作为DCs3。将受者随机分为DCs1、DCs2、DCs3及对照组,每组6只。术前24h,前3组分别注入1×106个DCs1、DCs2和DCs3,对照组不注射DCs。肾移植后观察各组移植肾存活时间,术后第20d检测受者脾细胞对负载供肾抗原及无关供者肾脏抗原DCs的反应。结果DCs1、DCs2,DCs3和对照组的移植肾存活时间分别为(8.1±0.8)d、(8.8±0.9)d、(62.1±13.7)d和(8.6±0.9)d。DCs1、DCs2组与对照组比较,差异无统计学意义(P>0.05),DCs3组与对照组比较,移植肾存活时间显著延长(P<0.01)。肾移植术后,DCs3组脾细胞对负载供肾抗原的DCs反应明显低于对照组(P<0.01),而对负载无关供者抗原的DCs反应与对照组比较,差异无统计学意义(P>0.05)。结论负载供肾抗原的受者DCs经CTLA-4Ig基因修饰后具有致耐受性,可以抑制受者对供者抗原的免疫反应,明显延长移植肾的存活时间。 相似文献
11.
Comparative histopathology of hepatic allografts and xenografts in the nonhuman primate 总被引:1,自引:0,他引:1
Y. Luo S. Kosanke L. Mieles T. Kobayashi S.F. Li M. Niekrasz A. Shimizu Y. Ye R.B. Colvin D.K.C. Cooper 《Xenotransplantation》1998,5(3):197-206
Abstract: Liver transplantation was performed in the following groups: Group 1, baboon-to-baboon allografting (n = 8) (control group); Group 2, ABO-compatible vervet monkey-to-baboon xenografting (n = 8); Group 3, ABO-incompatible vervet monkey-to-baboon xenografting (n = 6); Group 4, pig-to-baboon xenografting (n = 2); and Group 5, pig-to-rhesus monkey xenografting (n = 6). Immunosuppressive therapy (cyclosporine, cyclophosphamide, and methylprednisolone) was begun 2–7 days before liver transplantation (LTx) and continued indefinitely after LTx. The liver grafts were biopsied pre-LTx and subsequently post-LTx at approximately 1 hr, 2–3 hr, 7–10 days, 20–30 days, 60 days, 120 days, and at euthanasia or spontaneous death. There were 19 successful LTxs with grafts functioning from one hour to 123 days. No pig liver (Groups 4 and 5) survived more than 5.5 hr, as there was an immediate severe vascular response after reperfusion, typical of hyperacute rejection (congestion and hemorrhage). Vascular rejection was not seen in allografts (Group l), but early mild-to-moderate congestion and neutrophil infiltration were present in concordant xenografts (Groups 2 and 3), which were associated with moderate deposition of immunoglobulin, C3, and fibrinogen. Lymphoid cell infiltration, bile duct damage, and portal vein endothelialitis in the portal zones occurred later in both allografts (Group 1) and concordant xenografts (Groups 2 and 3), developing earlier in the presence of ABO-incompatibility (Group 3). In concordant xenografts it was usually followed by fibrosis. 相似文献
12.
Analyses of Peripheral Blood Mononuclear Cells in Operational Tolerance After Pediatric Living Donor Liver Transplantation 总被引:5,自引:0,他引:5
Ying Li Takaaki Koshiba Atsushi Yoshizawa Yukihide Yonekawa Kosuke Masuda Atsushi Ito Mikiko Ueda Takahide Mori Hiroshi Kawamoto Yoshimasa Tanaka Shimon Sakaguchi Nagahiro Minato Kathryn J. Wood Koichi Tanaka 《American journal of transplantation》2004,4(12):2118-2125
Operational tolerance (graft acceptance in an immunosuppression (IS)-free environment) after living-donor liver transplantation (LDLT) could occur by our elective protocol in some patients. There is, nevertheless, no reliable parameter to monitor patients who may discontinue IS without a risk of rejection. To identify such parameters, we systemically phenotyped peripheral blood mononuclear cells from operationally tolerant patients. An increase was observed in the frequency of CD4+CD25high+ cells, B cells and Vdelta1/Vdelta2 gammadeltaT-cells ratio in operationally tolerant patients (Gr-tol; n = 12), compared with those from age-matched volunteers (Gr-vol; n = 24) or patients on IS (Gr-IS; n = 19). The frequency of NK cells was decreased in Gr-tol, compared with those in Gr-IS or Gr-vol. The frequency of NKT cells was decreased after LDLT, compared with that in Gr-vol. Although the contribution of those subsets to the tolerant state remains elusive, the results may provide important clues for reliable indicators of tolerance after LDLT. 相似文献
13.
Christian A. Seiler E. L. Renner A. Czerniak D. Didonna Markus W. Büchler Jürg Reichen 《Transplant international》1999,12(3):195-201
Whereas early acute cellular rejection, even if successfully treated, seems to have an impact on late function and survival
of kidney and heart transplants, little quantitative data are available on its effect(s) on liver transplants. Routine liver
function tests, the functioning liver cell mass (galactose elimination capacity) and microsomal metabolic capacity (aminopyrine
breath test) were determined prospectively in 37 consecutive patients 1 year after liver transplantation. Of these, 19 (7
females and 12 males, 32–69 years of age) had previously required treatment for at least one biopsy proven acute cellular
rejection episode occuring a median 7 days after grafting, while 18 (6 females and 12 males, 30–67 years of age) had not.
The functioning liver cell mass and microsomal metabolic capacity were both within normal limits for the majority of patients
and did not differ significantly between patients with and without previous acute cellular rejection episodes. In contrast
to other solid organ transplants, early acute cellular rejection episodes do not affect late function of liver allografts
in man.
Received: 1 July 1998 Received in revised form 5 October 1999 Accepted: 12 October 1998 相似文献
14.
Stefan?Tange Marcus?N.?Scherer Christian?Graeb Joachim?Andrassy Martin?Justl Erika?Frank Karl-Walter?Jauch Edward?K.?Geissler
Paclitaxel is an anti-neoplastic drug that was recently shown also to have immunosuppressive properties in naïve rat heart transplant recipients. Here, we tested whether paclitaxel could also effectively reverse an ongoing immune response in transplant recipients. We therefore used a model in which Lewis rat recipients receiving ACI rat heterotopic heart allografts were: (1) untreated, or treated with either (2) paclitaxel or (3) cyclosporine, starting 5 days after transplantation. Allograft survival was determined in one group, and in a second group cytotoxic T-lymphocyte (CTL) responses were determined and serum anti-donor cytotoxic antibody levels were measured. Results showed that paclitaxel was as effective as cyclosporine in saving recipients from imminent allograft rejection. Immunologically, paclitaxel reduced the allogeneic-CTL response, but most impressively, the cytotoxic antibody response was nearly eliminated in saved recipients. Therefore, paclitaxel's immunosuppressive properties, along with its known effectiveness against a wide variety of tumors, makes it potentially useful for the simultaneous treatment of rejection and neoplasms in cases of transplant-related cancer. 相似文献
15.
Dendritic Cell Subset Ratio in Peripheral Blood Correlates with Successful Withdrawal of Immunosuppression in Liver Transplant Patients 总被引:8,自引:0,他引:8
George V. Mazariegos Alan F. Zahorchak Jorge Reyes Lynn Ostrowski Bridget Flynn Adriana Zeevi Angus W. Thomson 《American journal of transplantation》2003,3(6):689-696
Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage- cells that are further characterized as CD11c+ CD123-/lo (IL-3Ralpha-/lo) (pDC1) or as CD11c- CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 - similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression. 相似文献
16.
Prevention of allograft rejection by in vitro generated tolerogenic dendritic cells 总被引:10,自引:0,他引:10
Achieving immunological tolerance in transplantation has been a long sought-after goal since the 1960s. It is, therefore, interesting that the dendritic cells (DC), which are classically known as the most potent stimulators of T cell activation, are now also considered putative tools for tolerance induction. In line with this, much work has been performed using DC for vaccination and immune stimulation. Recently, great interest has been generated regarding the ability of DC to act as immune regulatory cells. Specific subsets of DC or immature DC (iDC) appear to be responsible for maintaining self-tolerance. In this review we will highlight our efforts at elucidating the contribution of DC in transplant tolerant in mice. Specifically, four strategies will be outlined that are currently being used for the generation of DC that have tolerogenic properties in the prevention of allograft rejection. The present study demonstrates that modulated iDC with blunted T cell stimulatory or antigen presentation abilities can afford transplant tolerance by minimizing T cell activation and proinflammatory cytokine production. Moreover, in an alternate strategy, normally matured DC have also been modulated such that alloreactive T cells are specifically targeted for deletion. 相似文献
17.
Koichi Urata Antoine Brault Bernard Rocheleau P.-M. Huet 《Transplant international》2000,13(6):420-427
Applying the orthotopic rat liver transplantation (ORLT) model, postoperative survival has been shown to be mainly dependent
on the portal vein clamping time (PVCT). It was hypothesized that prolonged intestinal congestion was responsible for the
activation of Kupffer cells (KC) with overproduction of TNF, secondary to splanchnic endotoxin accumulation and release on
reperfusion. The role of KCs was directly investigated in the context of long PVCTs by eliminating them (using liposome-encapsulated
dichloromethylene diphosphonate), by preventing their activation (using a calcium channel blocker, nisoldipine) and by inhibiting
TNF production (using thalidomide). Livers from different groups of rats were transplanted following 24-h cold preservation
in the UW solution with long PVCTs (from 18–21 min). KCs depletion, preservation with nisoldipine and pretreatment with thalidomide
significantly improved survival in conditions using long PVCTs. KC depletion and nisoldipine preservation had no effect on
liver enzymes or pathological findings while lung injury was significantly improved. The present data confirm that, in the
context of ORLT with long PVCTs, KCs are directly responsible for the systemic endotoxin-like shock syndrome and their effect
is mediated through overproduction of TNF.
Received: 30 August 1999 Revised: 18 May 2000 Accepted: 12 September 2000 相似文献
18.
19.
Mitsuo Shimada Katsuhiko Yanaga Keiji Kishikawa Saburo Kakizoe Hidetoshi Itasaka Tetsuo Ikeda Taketoshi Suehiro Keizo Sugimachi 《Transplant international》1993,6(1):4-7
Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4°C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511±216 vs 417±333 g/dl and 114.1±12.2 vs 91.4±12.2 mg/dl, respectively; P<0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability. 相似文献
20.
Horibe EK Sacks J Unadkat J Raimondi G Wang Z Ikeguchi R Marsteller D Ferreira LM Thomson AW Lee WP Feili-Hariri M 《Transplant immunology》2008,18(4):307-318
Clinically-applicable protocols that promote tolerance to vascularized skin grafts may contribute to more widespread use of composite tissue transplantation. We compared the properties of alloantigen (Ag)-pulsed, rapamycin (Rapa)-conditioned and control bone marrow-derived host myeloid dendritic cells (DCs) and their potential, together with transient immunosuppression (anti-lymphocyte serum+cyclosporine), to promote long-term, vascularized skin graft survival in Lewis rats across a full MHC barrier. Both types of DCs expressed low levels of CD86, but Rapa DC expressed lower levels of MHC II and CD40 and were less stimulatory in MLR. While both Rapa and control DCs produced low levels of IL-12p70 and moderate levels of IL-6 and IL-10 following TLR ligation, Rapa DC secreted significantly lower levels of IL-6 and IL-10 in response to LPS. Donor Ag-pulsed Rapa DC, but not control DC, induced long-term skin graft survival (median survival time >133 days) when administered 7 and 14 days post-transplant. Circulating T cells in hosts with long-surviving grafts were hyporesponsive to donor alloAg stimulation, but proliferated in response to third-party stimulation and produced IFN-gamma and IL-10. When recipients of long-surviving grafts were challenged with skin grafts, donor but not third-party grafts were prolonged, suggesting underlying regulatory mechanisms. Both flow cytometry and immunohistochemical analysis revealed that donor Ag-pulsed Rapa DC infusion expanded CD4+ Foxp3+ Treg in recipients' spleens, graft-associated lymph nodes and the graft. These data demonstrate for the first time that pharmacologically-modified, donor Ag-pulsed host DC administered post-transplant can promote indefinite vascularized skin graft survival, associated with Treg expansion. 相似文献