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Syngeneic Recipients (syngeneic + recipient)
Selected AbstractsL-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Chiara Uboldi Abstract L-selectin has been suggested to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we demonstrate that L-selectin,/, SJL mice are susceptible to proteolipid protein (PLP)-induced EAE because the compromised antigen-specific T cell proliferation in peripheral lymph nodes is fully compensated by the T cell response raised in their spleen. Transfer of PLP-specific T cells into syngeneic recipients induced EAE independent of the presence or absence of L-selectin on PLP-specific T cells or in the recipient. Leukocyte infiltration into the central nervous system parenchyma was detectable independent of the mode of disease induction and the presence or absence of L-selectin. In addition, we found L-selectin,/, C57BL/6 mice to be susceptible to myelin oligodendrocyte glycoprotein-induced EAE. Taken together, we demonstrate that in SJL and C57BL/6 mice L-selectin is not required for EAE pathogenesis. The apparent discrepancy of our present observation to previous findings, demonstrating a role of L-selectin in EAE pathogenesis in C57BL/6 mice or myelin-basic protein (MBP)-specific TCR-transgenic B10.PL mice, may be attributed to background genes rather than L-selectin and to a unique role of L-selectin in EAE pathogenesis in MBP-TCR-transgenic mice. [source] Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantationJOURNAL OF PINEAL RESEARCH, Issue 4 2009Zhanqing Li Abstract:, Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine,Tryptophan,Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39,71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity. [source] The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injuryLIVER TRANSPLANTATION, Issue 8 2008Constantino Fondevila Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(,) rats were harvested, stored for 24 hours at 4°C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+),C6(+), (2) C6(+),C6(,), (3) C6(,),C6(+), and (4) C6(,),C6(,). At day +1, C6(,) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 ± 0.9, 7.3 ± 1.3, 4.5 ± 0.6, and 4.8 ± 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(,) grafts (serum glutamic oxaloacetic transaminase: 2573 ± 488, 1808 ± 302, 1170 ± 111, and 1188 ± 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(,) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-,, interleukin-1,, and tumor necrosis factor messenger RNA/protein was also reduced in C6(,) OLTs in comparison with C6(+) OLTs. Western blot,assisted expression of proapoptotic caspase-3 was decreased in C6(,) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(,) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase,mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(,) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. Liver Transpl 14:1133,1141, 2008. © 2008 AASLD. [source] Differences in lymphocyte gene expression between tolerant and syngeneic liver grafted ratsLIVER TRANSPLANTATION, Issue 3 2004Masayuki Fujino Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. We have taken the advantage of DNA microarray technology to investigate gene expression mechanism in regulatory cells. In the present study, using a tacrolimus (FK506) induced tolerance of the fully mismatched liver allograft rat model, we demonstrated that, in contrast with peripheral blood lymphocytes (PBLs) from syngeneic recipients, PBLs taken from tolerant recipients 100 days after transplantation were able to suppress the in vitro proliferation of allogeneic PBLs and to prolong the survival of second syngeneic recipients. We also compared messenger RNA profiles in PBLs from tolerant recipients with those from syngeneic recipients using a DNA microarray with probe sets corresponding to more than 8000 rat genes. There were 96 up-regulated and 103 down-regulated genes in the tolerant recipients. In the up-regulated group, there were 76 known genes and 20 expressed sequence tags (ESTs). In the down-regulated groups, there were 87 known genes and 16 ESTs. Our data indicated that FK506 treatment induced tolerance and expansion of regulatory cells and the DNA microarray technology was useful for this application and provided many informative insights into the mechanism of lymphocyte regulation. (Liver Transpl 2004;10:379,391.) [source] Cryopreservation of vascularized ovary: An evaluation of histology and function in ratsMICROSURGERY, Issue 5 2008Shijie Qi M.D. Cryopreservation of organs has been investigated to sustain the reproductive function of patients undergoing sterilizing chemotherapy and radiotherapy or reproductive surgery. A modified protocol for whole organ cryopreservation was described and the outcome of cryopreservative ovaries was evaluated, and apoptosis of cryopreservative cells stored for different time period and the viability of cryopreserved cells stored at different temperature was examined in rats. Lewis rat ovarian grafts were perfused for 30 min at 0.35 ml/min with M2 medium containing 0.1M fructose and increasing concentrations of 0,1.5M dimethylsulfoxide, cooled to ,140°C controlled by a computerized program, and stored in liquid nitrogen (,196°C) for 24 hours. After being thawed, ovaries were transplanted to syngeneic recipients after bilateral oophorectomy. Graft functions were monitored postoperatively. The major findings were that: 1) A 100% survival rate of rat ovaries was achieved in this study. Ovarian hormone secretion recovered in 80% rats which had received cryopreservative ovarian grafts. Postoperative serum estradiol levels in the cryopreservative graft group were lower than in the sham surgery control, but much higher than in the bilateral oophorectomy group. 2) Histological examination of cryopreservative ovarian grafts showed preantral and antral follicles. Two gestations were obtained. 3) Estradiol levels remained low in ovariectomized rats while in the oophorectomized rats given cryopreservative ovarian grafts levels started to rise after 14 ± 3 days. 4) The average viability in the cells from cryopreservative ovary organ (,196°C) was about 71 ± 18% compared to 90 ± 9% of fresh cells. This success should encourage further improvement of cryopreservative techniques for large organs. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source] Prevention of red cell alloimmunization by CD25 regulatory T cells in mouse modelsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2007Jin Yu Transfusion therapy is currently an effective therapeutic intervention in a number of diseases, including sickle cell disease. However, its use is complicated by a high incidence of red blood cell (RBC) alloimmunization in the transfusion recipients. The identification of T regulatory cells (Tregs) among the CD4+ CD25+ T cell subset as key regulators of peripheral tolerance in mice as well as humans has opened an exciting era in the prevention and treatment of autoimmune disease and for improving organ transplantation. However, their potential in inducing transfusion tolerance remains to be explored. We used red cells from mice transgenic for human glycophorin A blood group antigen as donor cells and transfused wild-type mice to induce alloantibodies, as an experimental system to study RBC alloimmunization. We found that depletion with anti-CD25 enhanced the alloantibody production, indicating that CD25 Tregs play an important role in regulation of alloantibody responses. More importantly, adoptive transfer of purified population of CD4+CD25+ but not CD4+CD25, cells from naïve mice prevented the induction of IgG and IgM alloantibody production in transfusion recipients, with a concomitant reduction in activated splenic B cells and macrophages. Similarly, adoptive transfer of purified populations of CD4+CD25+ cells from naïve mice into naïve syngeneic recipients inhibited the anti-Ig response to rat RBCs in the recipients but transfer of control CD4+CD25, cells did not. Altogether, our results demonstrate that Tregs participate in the control of transfusion-associated RBC alloantibody responses, opening up the possibility that Treg immunotherapy may be exploited for suppressing transfusion immunization events. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Diannexin, a Novel Annexin V Homodimer, Protects Rat Liver Transplants Against Cold Ischemia-Reperfusion InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2007X.-D. Shen Ischemia/reperfusion injury (IRI) remains an important problem in clinical transplantation. Following ischemia, phosphatidylserine (PS) translocates to surfaces of endothelial cells (ECs) and promotes the early attachment of leukocytes/platelets, impairing microvascular blood flow. Diannexin, a 73 KD homodimer of human annexin V, binds to PS, prevents attachment of leukocytes/platelets to EC, and maintains sinusoidal blood flow. This study analyzes whether Diannexin treatment can prevent cold IRI in liver transplantation. Rat livers were stored at 4°C in UW solution for 24 h, and then transplanted orthotopically (OLT) into syngeneic recipients. Diannexin (200 ,g/kg) was infused into: (i) donor livers after recovering and before reperfusion, (ii) OLT recipients at reperfusion and day +2. Controls consisted of untreated OLTs. Both Diannexin regimens increased OLT survival from 40% to 100%, depressed sALT levels, and decreased hepatic histological injury. Diannexin treatment decreased TNF-,, IL-1,, IP-10 expression, diminished expression of P-selectin, endothelial ICAM-1, and attenuated OLT infiltration by macrophages, CD4 cells and PMNs. Diannexin increased expression of HO-1/Bcl-2/Bcl-xl, and reduced Caspase-3/TUNEL+ apoptotic cells. Thus, by modulating leukocyte/platelet trafficking and EC activation in OLTs, Diannexin suppressed vascular inflammatory responses and decreased apoptosis. Diannexin deserves further exploration as a novel agent to attenuate IRI, and thereby improve OLT function/increase organ donor pool. [source] Tissue targeting of anti-RNP autoimmunity: Effects of T cells and myeloid dendritic cells in a murine modelARTHRITIS & RHEUMATISM, Issue 2 2009Eric L. Greidinger Objective To explore the role of immune cells in anti-RNP autoimmunity in a murine model of pneumonitis or glomerulonephritis, using adoptive transfer techniques. Methods Donor mice were immunized with 50 ,g of U1,70-kd small nuclear RNP fusion protein and 50 ,g of U1 RNA adjuvant. Whole splenocytes as well as CD4+ cell and dendritic cell (DC) subsets from the immunized mice were infused into naive syngeneic recipients. Anti-RNP and T cell responses were assessed by immunoblotting, enzyme-linked immunosorbent assay, and flow cytometry. Development of renal or lung disease was assessed by histology and urinalysis. Results Unfractionated splenocytes from donor mice without proteinuria induced predominantly lung disease in recipients (8 [57%] of 14 versus 2 [14%] of 14 developing renal disease; P = 0.046). However, infusion of CD4+ cells from donors without proteinuria induced renal disease more frequently than lung disease (7 [70%] of 10 versus 2 [20%] of 10; P = 0.01); adoptive transfer of RNP+CD4+ T cells from short-term culture yielded similar results (renal disease in 8 [73%] of 11 recipients versus lung disease in 3 [27%] of 11). Cotransfer of splenic myeloid DCs and CD4+ T cells from immunized donors prevented induction of renal disease in all 5 recipients (P = 0.026 versus recipients of fresh CD4+ cells alone), although lung disease was still observed in 1 of 5 mice. Transfer of myeloid DCs alone from immunized donors induced lung disease in 3 (60%) of 5 recipients, without evidence of nephritis. Cotransfer of splenocytes from mice with and those without nephritis led to renal disease in 4 of 5 recipients, without evidence of lung disease. Conclusion These findings indicate that RNP+CD4+ T cells are sufficient to induce anti-RNP autoimmunity, tissue targeting in anti-RNP autoimmunity can be deviated to either a renal or pulmonary phenotype depending on the presence of accessory cells such as myeloid DCs, and DC subsets can play a role in both propagation of autoimmunity and end-organ targeting. [source] | ||||||||||