%0 Journal Article
%~ PubMed
%A Rahman, Wassim
%A Huang, Pauline
%A Belov, Larissa
%A Chrisp, Jeremy S
%A Christopherson, Richard I
%A Stapelberg, Peter M
%A Warner, Fiona J
%A George, Jacob
%A Bowen, David G
%A Strasser, Simone I
%A Koorey, David
%A Sharland, Alexandra F
%A McCaughan, Geoffrey W
%A Shackel, Nicholas A
%T Analysis of human liver disease using a cluster of differentiation (CD) antibody microarray.
%B Liver International
%D 2012
%C United States
%I Wiley-Blackwell Publishing, Inc.
%V 32
%N 10
%P 1527-1534
%@ 1478-3231
%X BACKGROUND: A CD antibody microarray has been previously developed allowing semi-quantitative identification of greater than 80 CD antigens on circulating leucocytes from peripheral blood samples. This assay, which uses a live cell-capture technique, enables an extensive leucocyte immunophenotype determination in a single analysis and to date this has been used successfully to characterise diseases including human leukaemias and HIV infection. AIMS: To determine CD antigen expression profiles for patients with various liver diseases and to look for preserved disease-specific signatures. METHODS: Three liver disease groups including hepatitis C (HCV) (n??=??35), non-alcoholic steatohepatitis (NASH) (n??=??21) and alcohol-related liver disease (n??=??14) were compared with a normal group (n??=??23). Hierarchal Clustering (HCL) and Principal Component Analysis (PCA) of the data revealed distinct binding patterns for patients with and without cirrhosis. RESULTS: Patients with cirrhosis and portal hypertension compared with those without cirrhosis had significantly reduced expression of several markers of T-cell function including CD45, CD8, CD28 and TCR ??/??. Disease prediction algorithms based on the expression data were able to discriminate cirrhotics from non-cirrhotics with 71% overall success, which improved to 77% when only patients with HCV were considered. CONCLUSIONS: These results demonstrate disease-specific consensus patterns of expression of CD antigens for patients with chronic liver disease, suggesting that the CD antibody array is a promising tool in the analysis of human liver disease, and with further refinement may have future research and clinical utility.
%Z FOR Codes: 110704 100402 110307


%0 Journal Article
%~ PubMed
%A Ganbold, Anar
%A Andersen, Sean
%A Tay, Szun S
%A Cunningham, Eithne
%A Ilie, Victor
%A Krishnan, Sai
%A Wang, C
%A McCaughan, Geoffrey W
%A Sharland, Alexandra F
%A Bishop, G Alex
%T Expression of common gamma chain signalling cytokines and their receptors distinguishes rejection from tolerance in a rat organ transplant model.
%B Transplant Immunology
%D 2012
%C Netherlands
%I Elsevier BV
%V 27
%N 2-3
%P 89-94
%@ 1878-5492
%X BACKGROUND: Signalling through the cytokine common ?? chain (??c) is crucial for survival of activated T cells. In its absence, severe combined immunodeficiency ensues and transplanted tissues are not rejected. METHODS: To determine whether differences in the availability of ??c signalling cytokines correlate with rejection or acceptance, we examined expression of all ??c signalling components in organs transplanted between PVG donors and DA recipients. In this combination hearts or kidneys are rejected in <10days while livers survive >100days. Expression of the ??c cytokines IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 and their receptors ??c, IL-2R??, IL-2R??/IL-15R??, IL-4R??, IL-7R??, IL-9R??, IL-15R?? and IL-21R?? was determined by real-time PCR pre-transplant and on days 3, 5 and 7 after transplantation. RESULTS: Most increased after transplantation, although there were significantly lower levels of IL-2, IL-2R??, IL-4 and IL-15R?? in tolerant livers compared to rejecting hearts or kidneys. IL-9 was only expressed in normal kidneys and decreased during rejection. IL-15 was constitutively expressed and did not change after transplantation. IL-21 and IL-21R increased in all transplanted organs to a similar extent. IL-7R?? in liver was considerably increased compared with heart or kidney, consistent with its known inverse relationship to global levels of ??c signalling. CONCLUSIONS: In transplanted livers, acceptance is associated with low levels of all ??c cytokines or receptors except IL-21. This is consistent with "dilution" of ??c cytokines from a finite clone size of alloreactive T cells in livers, which are ten times larger than kidneys or hearts.
%Z FOR Codes: 1104 1109


%0 Book Section
%A Sharland, Alexandra
%T Pancreatic beta-cell failure in the pathogenesis of type 1 diabetes
%B A Modern Epidemic
%D 2012
%C Australia
%I Sydney University Press
%V 
%N 
%P 70-86
%@ 9781920899851
%E Twigg, Stephen
%E Magnusson, Roger S
%E Baur, Louise
%X 
%Z FOR Codes: 110306 60104


%0 Journal Article
%~ PubMed
%A Cubitt, Jonathan
%A Pennington, Thomas
%A Wang, Chuanmin
%A Allen, Richard
%A Bishop, Alex
%A Sharland, Alexandra
%T Reliable and reproducible murine models for commonly used abdominal plastic surgical flaps.
%B Journal of Reconstructive Microsurgery
%D 2012
%C United States
%I Thieme Medical Publishers
%V 28
%N 3
%P 161-166
%@ 1098-8947
%X Animal models have been used for many years in surgical research to develop different surgical techniques, improve understanding of anatomy and physiology and hone surgical skills. The benefit of such models has been particularly important in developing relatively young specialties like plastic surgery and many plastic surgical techniques are designed and studied in animals long before they are used in humans. We describe techniques for raising several reliable and reproducible abdominal flaps in rodents, including transverse rectus abdominis myocutaneous flaps in rats and mice, superficial inferior epigastric artery flaps in rats and perforator flaps in rats. The intention of this paper is to act as a point of reference for any microvascular or plastic surgeon who is planning to perform abdominal plastic surgical flap research or further microvascular skills.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Bishop, G Alex
%A Ierino, Francesco L
%A Sharland, Alexandra F
%A Hall, Bruce M
%A Alexander, Stephen I
%A Sandrin, Mauro S
%A Coates, P Toby
%A McCaughan, Geoffrey W
%T Approaching the Promise of Operational Tolerance in Clinical Transplantation.
%B Transplantation
%D 2011
%C United States
%I Lippincott Williams & Wilkins
%V 91
%N 10
%P 1065-1074
%@ 0041-1337
%X Long-term acceptance of transplanted organs without requirement for indefinite immunosuppression remains the ultimate goal of transplant clinicians and scientists. This clinical state of allograft acceptance termed "operational tolerance" has been elusive in routine practice. However, there are published reports of recipients where immunosuppression has been discontinued, by intention or patient noncompliance, in which the outcome is a nondestructive immune response and normal function. The question now arises how clinical operational tolerance might be achieved in the majority of recipients. This review provides an overview of current approaches to achieve operational tolerance, including the use of donor bone marrow and depletion of recipient T cells and the resistance of liver transplants to rejection. It also describes the key role of clinical immune monitoring and future approaches to tolerance induction including inhibition of T-cell signaling, manipulation of costimulatory pathways, and expansion of regulatory T cells. The principles of these experimental approaches may ultimately be extended to provide safe and effective control of transplant rejection and induction of clinical operational tolerance.
%Z FOR Codes: 111403


%0 Journal Article
%~ PubMed
%A Bishop, G Alex
%A Sharland, Alexandra F
%A Ierino, Francesco L
%A Sandrin, Mauro S
%A Hall, Bruce M
%A Alexander, Stephen I
%A Coates, P Toby
%A McCaughan, Geoffrey W
%T Operational Tolerance in Organ Transplantation Versus Tissue Engineering: Into the Future.
%B Transplantation
%D 2011
%C United States
%I Lippincott Williams & Wilkins
%V 92
%N 8
%P e39
%@ 0041-1337
%X 
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Wang, Chuanmin
%A Cordoba, Shaun
%A Hu, Min
%A Bertolino, Patrick
%A Bowen, David G
%A Sharland, Alexandra F
%A Allen, Richard D M
%A Alexander, Stephen I
%A McCaughan, Geoffrey W
%A Bishop, G Alex
%T Spontaneous acceptance of mouse kidney allografts is associated with increased Foxp3 expression and differences in the B and T cell compartments.
%B Transplant immunology
%D 2011
%C Netherlands
%I Elsevier BV
%V 24
%N 3
%P 149-56
%@ 1878-5492
%X Spontaneous acceptance of organ allografts can identify novel mechanisms of drug-free transplantation tolerance. Spontaneous acceptance occurs in both mouse kidney transplants and rat liver transplants however the early immune processes of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain kidney allografts in fully MHC-incompatible B10.BR recipients was compared with rejection (REJ) of heart allografts in the same strain combination. Graft infiltrate and antibody deposition were examined by immunohistochemical staining. Expression of mRNA was measured by quantitative real-time PCR. Apoptosis was examined by TUNEL staining. The majority of kidney allografts were accepted long-term and induced tolerance (TOL) of donor-strain skin grafts, showing that acceptance was not due to immune ignorance. There was an extensive infiltrate of T cells in the TOL kidney that exceeded the level in REJ hearts but subsequently declined. The main differences were deposition of IgG2a antibody in REJ that was absent in TOL, more B cells infiltrating TOL kidneys and a progressive increase in the ratio of CD8:CD4 cells during rejection. There was also significantly greater Foxp3 mRNA expression in TOL. Kidneys from RAG-/- donors were accepted, showing that donor lymphocytes were not necessary for acceptance. Neutralising antibodies to TGF-?? administered from day 0 to day 6 did not prevent TOL. On the basis of cytokine expression and apoptosis there was no evidence for immune deviation or deletion as mechanisms of acceptance. In accord with the findings of spontaneous acceptance of liver allografts in rats, the main difference between mouse kidney TOL and heart REJ was in the B cell compartment. The major difference to rat liver allograft acceptance was that apoptosis of infiltrate did not appear to play a role. Instead, increased Foxp3 expression in TOL kidneys implies that regulatory T cells might be important.
%Z FOR Codes: 1103 1107


%0 Journal Article
%~ PubMed
%A Chen, Gang Eric
%A Wu, Huiling
%A Ma, Jin
%A Chadban, Steven J
%A Sharland, Alexandra
%T Toll-like receptor 4 engagement contributes to expression of NKG2D ligands by renal tubular epithelial cells.
%B Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
%D 2011
%C United Kingdom
%I Oxford University Press
%V 26
%N 12
%P 3873-81
%@ 1460-2385
%X Engagement of Toll-like receptor (TLR) 4 on intrinsic kidney cells is critical for the full development of renal ischaemia-reperfusion injury (IRI). Effects of TLR signalling in renal parenchymal cells include the production of cytokines, chemokines and other soluble mediators which contribute to local inflammation and leucocyte accumulation. Whether engagement of TLR4 on kidney cells results in additional pro-inflammatory modifications of the renal microenvironment remains to be determined.
%Z FOR Codes: 1107


%0 Journal Article
%~ PubMed
%A Wang, Chuanmin
%A Tay, Szun Szun
%A Tran, Giang T
%A Hodgkinson, Suzanne J
%A Allen, Richard D M
%A Hall, Bruce M
%A McCaughan, Geoffrey W
%A Sharland, Alexandra F
%A Bishop, G Alex
%T Donor IL-4 treatment induces alternatively activated liver macrophages and IDO-Expressing NK cells and promotes rat liver allograft acceptance.
%B Transplant immunology
%D 2010
%C Netherlands
%I Elsevier BV
%V 22
%N 3-4
%P 172-8
%@ 1878-5492
%X Most approaches to transplant tolerance involve treatment of the recipient to prevent rejection. This study investigates donor treatment with IL-4 for its effect on subsequent rat liver allograft survival. Rat orthotopic liver transplants were performed in rejecting (PVG donor to Lewis recipient) or spontaneously tolerant (PVG to DA) strain combinations. Donors were untreated or injected intraperitoneally with IL-4 (30,000U/day) for 5days. Tissue infiltrates and gene expression were examined by immunohistochemistry and real-time quantitative PCR. IL-4 induced a marked leukocyte infiltrate in donor livers prior to transplant. Macrophages comprised the major population, although B cells, T cells and natural killer (NK) cells also increased. IL-4-induced liver macrophages had an alternatively activated phenotype with increased expression of mannose receptor but not inducible nitric oxide synthase (NOS2). IL-4 also induced IDO and IFN-gamma expression by NK cells. Donor IL-4-treatment converted rejection to acceptance in the majority of Lewis recipients (median survival time >96days) and did not prevent acceptance in DA recipients. Acceptance in Lewis recipients was associated with increased donor cell migration to recipient spleens and increased splenic IL-2, IFN-gamma and IDO expression 24h after transplantation. Donor IL-4-treatment increased leukocytes in the donor liver including potentially immunosuppressive populations of alternatively activated macrophages and IDO-expressing NK cells. Donor treatment led to long-term acceptance of most livers in association with early immune activation in recipient lymphoid tissues.
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Sharland, Alexandra
%A Logan, Grant J
%A Bishop, Alex
%A Alexander, Ian E
%T Liver-directed gene expression using recombinant AAV 2/8 vectors -- a tolerogenic strategy for gene delivery?
%B Discovery Medicine
%D 2010
%C United States
%I Solariz, Inc.
%V 9
%N 49
%P 519-527
%@ 1944-7930
%X Vectors based on recombinant adeno-associated virus (AAV) 2/8 hold considerable promise for use in human gene therapy. These vectors are safe, and have minimal immunostimulatory properties. Their combination with efficient, liver-specific promoters allows high-level transgene expression in the hepatocytes of small and large animals. In small animal models, this high level of liver expression results in tolerance to the transgene products. Tolerance to transgene products may also be achievable using these vectors for human gene therapy, but the HLA diversity (and thus variability in T cell recognition of transgene products) and high frequency of prior natural exposure to AAV in human populations impose additional challenges that must be overcome in order for this strategy to succeed.
%Z FOR Codes: 100401


%0 Journal Article
%~ PubMed
%A Sharland, Alexandra
%A Gorrell, Mark D
%T Cooperation of innate and adaptive immunity in the pathogenesis of biliary atresia: There's a killer on the run.
%B Hepatology (Baltimore, Md.)
%D 2009
%C United States
%I John Wiley
%V 50
%N 6
%P 2037-40
%@ 1527-3350
%X 
%Z FOR Codes: 110707 110307 110804


%0 Journal Article
%~ PubMed
%A Laurence, Jerome M
%A Allen, Richard D M
%A McCaughan, Geoffrey W
%A Logan, Grant J
%A Alexander, Ian E
%A Bishop, G Alex
%A Sharland, Alexandra F
%T Gene therapy in transplantation.
%B Transplantation Reviews
%D 2009
%C United States
%I WB Saunders Co.
%V 23
%N 3
%P 159-170
%@ 1557-9816
%X Gene therapy is an exciting and novel technology that offers the prospect of improving transplant outcomes beyond those achievable with current clinical protocols. This review explores both the candidate genes and ways in which they have been deployed to overcome both immune and non-immune barriers to transplantation success in experimental models. Finally, the major obstacles to implementing gene therapy in the clinic are considered.
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Obeidy, Peyman
%A Sharland, Alexandra F
%T Molecules in Focus NKG2D and its ligands.
%B The international journal of biochemistry & cell biology
%D 2009
%C United Kingdom
%I Pergamon
%V 41
%N 12
%P 2364-7
%@ 1357-2725
%X NKG2D is an activating immunoreceptor, first recognized on NK cells but subsequently found on gammadelta T cells, CD8(+) alphabeta T cells and macrophages. In NK cells, inhibitory signals are generally dominate over activating signals. However, activating signals mediated through engagement of NKG2D by its ligands on target cells can bypass signals transmitted through inhibitory NK receptors, allowing NKG2D to function as a "master-switch" in determining the activation status of NK cells. NKG2D is important for T cell and NK cell-mediated immunity to viruses and tumours, and has roles in autoimmune disease, allogeneic transplantation, and xenotransplantation. Depending upon the situation, development of strategies to either block or to enhance the interactions between NKG2D and its ligands may have important implications for human health and disease.
%Z FOR Codes: 110707 60106


%0 Journal Article
%~ PubMed
%A Laurence, Jerome M
%A Wang, Chuanmin
%A Zheng, Maolin
%A Cunningham, Sharon
%A Earl, John
%A Tay, Szun Szun
%A Allen, Richard D M
%A McCaughan, Geoffrey W
%A Alexander, Ian E
%A Bishop, G Alex
%A Sharland, Alexandra F
%T Overexpression of indoleamine dioxygenase in rat liver allografts using a high-efficiency adeno-associated virus vector does not prevent acute rejection.
%B Liver Transplantation
%D 2009
%C United States
%I John Wiley & Sons, Inc.
%V 15
%N 2
%P 233-241
%@ 1527-6473
%X The aim of this study was to evaluate the ability of local overexpression of indoleamine dioxygenase (IDO) to abrogate rat liver transplant rejection by the use of an adeno-associated virus vector [recombinant adeno-associated virus 2/8 (rAAV2/8)] to deliver the transgene to the allograft prior to transplantation. A green fluorescent protein (GFP)-expressing vector [recombinant adeno-associated virus 2/8-liver-specific promoter 1-enhanced green fluorescent protein (rAAV2/8-LSP1-eGFP)] was used to examine the kinetics of expression and optimal dosing for transduction of Piebald Virol Glaxo (PVG) rat livers. A vector encoding the rat IDO gene (rAAV2/8-LSP1-rIDO) was constructed and tested by its ability to induce tryptophan catabolism and kynurenine production in vitro and in vivo. PVG donor rats were injected, via the portal vein, with rAAV2/8-LSP1-rIDO 2 weeks before transplantation into PVG strain isograft or Lewis (LEW) strain allograft recipients. With the enhanced GFP vector, 29.5% and 47.4% of hepatocytes were found to express GFP at 3 and 6 weeks after injection, respectively. In untransplanted PVG animals, the rAAV2/8-LSP1-rIDO vector induced, 3 weeks after administration, a 1.8-fold increase (P = 0.0161) in liver IDO activity, which was associated with a fall in serum tryptophan to 0.5 times the baseline level (P < 0.001). PVG recipients of PVG liver isografts pretreated with the IDO-expressing vector had a 45% lower level of serum tryptophan than recipients of isografts pretreated with the GFP-expressing vector (P = 0.03). LEW recipients of PVG liver allografts pretreated with the rat IDO vector had a median survival time of 12 days, whereas recipients of allografts pretreated with rAAV2/8-LSP1-eGFP had a median survival time of 13 days (P = 0.38). Both groups displayed similar histological features of acute cellular rejection. In conclusion, rAAV2/8 vectors produce highly efficient, though delayed, hepatocyte transduction in vivo and provide a useful gene delivery tool for transplantation models. However, gene delivery using IDO was unsuccessful in prolonging rat liver allograft survival.
%Z FOR Codes: 110708 100401


%0 Journal Article
%~ PubMed
%A Laurence, Jerome M
%A Wang, Chuanmin
%A Park, Euiyoun T
%A Buchanan, Alexandra
%A Clouston, Andrew
%A Allen, Richard D M
%A Mccaughan, Geoffrey W
%A Bishop, G Alex
%A Sharland, Alexandra F
%T Blocking indoleamine dioxygenase activity early after rat liver transplantation prevents long-term survival but does not cause acute rejection.
%B Transplantation
%D 2008
%C United States
%I Lippincott Williams & Wilkins, Inc.
%V 85
%N 9
%P 1357-1361
%@ 0041-1337
%X In a well-characterized rat model of liver transplantation, Piebald Virol Glaxo strain livers are accepted long term in fully mismatched Dark Agouti recipients (tolerance; TOL), but rejected in Lewis recipients (rejection; REJ). Spontaneous tolerance induction is associated with increased interferon-gamma expression, and we examined the role of the interferon-gamma-inducible immunomodulatory enzyme indoleamine dioxygenase (IDO) in this model. On day 3 after transplantation, IDO expression in the spleen of TOL recipients was significantly greater than in REJ. The B-cell population accounted for this early IDO increase. Intragraft expression of IDO increased to the same extent in both TOL and REJ. IDO inhibition for 7 days after transplantation reduced survival, but did not cause acute rejection of the liver in the TOL model. In conclusion, the differential IDO expression by B lymphocytes in the spleen of TOL recipients is not critical for preventing acute rejection.
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Lam, Vincent W T
%A Taylor, Claire F
%A Laurence, Jerome M
%A Wang, Chuanmin
%A Sharland, Alexandra F
%A McCaughan, Geoffrey W
%A Hodgkinson, Suzanne
%A Allen, Richard D M
%A Hall, Bruce M
%A Bishop, G Alex
%T Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats: Effect on foxp3 and cytokine expression and graft infiltration.
%B Transplant Immunology
%D 2008
%C Netherlands
%I Elsevier BV
%V 19
%N 1
%P 20-24
%@ 0966-3274
%X The ability of anti-T cell monoclonal antibody G4.18 and polyclonal anti-lymphocyte serum (ALS) to induce long-term graft survival was examined in a high-responder rat heart transplant model. Heterotopic heart allografts were performed from PVG rat strain donors to high-responder Lewis recipients. Immunosuppressive properties of G4.18 and ALS were investigated by immunohistochemistry and PCR analysis. Untreated graft rejection was 8.5 days while treatment with 1 ml ALS prolonged survival to 11.5 days (p=0.01). Treatment with 7 mg/kg G4.18 on days 1 and 3 prolonged survival to >100 days (p=0.002 vs. control and p=0.002 vs. ALS) but did not induce tolerance. Acceptance was associated with marked inhibition of cellular infiltration and inflammatory cytokine expression and only a brief, slight increase in Foxp3:T cell ratio in the graft and no increase in the spleen. In conclusion, G4.18 treatment led to long-term heart transplant survival associated with marked inhibition of early inflammation. Failure to develop tolerance was associated with a lack of early accumulation of Foxp3 cells in the graft or spleen.
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Tran, Peter D
%A Christiansen, Dale
%A Winterhalter, Adam
%A Brooks, Andrew
%A Gorrell, Mark
%A Lilienfeld, Benjamin G
%A Seebach, Jörg D
%A Sandrin, Mauro
%A Sharland, Alexandra
%T Porcine cells express more than one functional ligand for the human lymphocyte activating receptor NKG2D.
%B Xenotransplantation
%D 2008
%C Denmark
%I Wiley-Blackwell Munksgaard
%V 15
%N 5
%P 321-32
%@ 1399-3089
%X Xenotransplantation could ameliorate the severe shortage of donor organs. The initial results of transplantation from genetically-modified pig donors to primate recipients suggest that hyperacute rejection can be overcome, but thrombotic microangiopathy and the human anti-pig cellular immune response remain as significant impediments to successful clinical xenotransplantation. NKG2D is an activating immunoreceptor found on human natural killer (HuNK) cells, CD8(+) and gammadelta T cells. Signaling through NKG2D mediates cytotoxicity and cytokine secretion by NK cells and co-stimulation of T cells.
%Z FOR Codes: 110702 110312


%0 Journal Article
%~ PubMed
%A Sharland, Alexandra
%T The inhaled route to improved liver function.
%B Hepatology (Baltimore, Md.)
%D 2008
%C United States
%I John Wiley & Sons Inc.
%V 47
%N 2
%P 755-756
%@ 0270-9139
%X 
%Z FOR Codes: 110307


%0 Journal Article
%~ PubMed
%A Tovey, E R
%A Kemp, A S
%A Almqvist, C
%A Sharland, A
%A Marks, G B
%T Do immune responses to inhaled skin flakes modulate the expression of allergic disease?
%B Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
%D 2007
%C United Kingdom
%I Blackwell Publishing Ltd
%V 37
%N 8
%P 1199-1203
%@ 0954-7894
%X We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the ''hygiene hypothesis'', is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co-exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Wu, Huiling
%A Chen, Gang
%A Wyburn, Kate R
%A Yin, Jianlin
%A Bertolino, Patrick
%A Eris, Josette M
%A Alexander, Stephen I
%A Sharland, Alexandra F
%A Chadban, Steven J
%T TLR4 activation mediates kidney ischemia/reperfusion injury.
%B The Journal of clinical investigation
%D 2007
%C US
%I American Society for Clinical Investigation
%V 117
%N 10
%P 2847-59
%@ 0021-9738
%X Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we demonstrated a significant increase in TLR4 expression by tubular epithelial cells (TECs) and infiltrating leukocytes within the kidney following ischemia. TLR4 signaling through the MyD88-dependent pathway was required for the full development of kidney IRI, as both TLR4(-/-) and MyD88(-/-) mice were protected against kidney dysfunction, tubular damage, neutrophil and macrophage accumulation, and expression of proinflammatory cytokines and chemokines. In vitro, WT kidney TECs produced proinflammatory cytokines and chemokines and underwent apoptosis after ischemia. These effects were attenuated in TLR4(-/-) and MyD88(-/-) TECs. In addition, we demonstrated upregulation of the endogenous ligands high-mobility group box 1 (HMGB1), hyaluronan, and biglycan, providing circumstantial evidence that one or more of these ligands may be the source of TLR4 activation. To determine the relative contribution of TLR4 expression by parenchymal cells or leukocytes to kidney damage during IRI, we generated chimeric mice. TLR4(-/-) mice engrafted with WT hematopoietic cells had significantly lower serum creatinine and less tubular damage than WT mice reconstituted with TLR4(-/-) BM, suggesting that TLR4 signaling in intrinsic kidney cells plays the dominant role in mediating kidney damage.
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Sadeghi, A.
%A Xiao, C.
%A Sharland, A. F.
%A Allen, R. D. M.
%A McCaughan, G. W.
%A Bishop, G. A.
%T Cytokine common gamma chain expression and its relation to liver transplant tolerance and rejection in a rat model.
%B Immunology and Cell Biology
%D 2006
%C UK
%I Nature Publishing Group
%V 84
%N 3
%P A27-A28
%@ 0818-9641
%X 
%Z FOR Codes: 110708


%0 Journal Article
%~ Isi
%A Tran, P.
%A Hing, A.
%A Hicks, M.
%A Gao, L.
%A Faddy, S.
%A Kesteven, S.
%A Stewart, G.
%A Macdonald, P.
%A Sharland, A.
%T Expression of NKG2D ligands following brain-death.
%B Immunology and Cell Biology
%D 2006
%C Australia
%I Blackwell Publishing Asia
%V 84
%N 3
%P A10-A10
%@ 0818-9641
%X 
%Z FOR Codes: 110708 110323


%0 Journal Article
%~ PubMed
%A Cordoba, Shaun P
%A Wang, Chuanmin
%A Williams, Rohan
%A Li, Jian
%A Smit, Lynn
%A Sharland, Alexandra
%A Allen, Richard
%A McCaughan, Geoffrey
%A Bishop, Alex
%T Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction.
%B Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
%D 2006
%C United States
%I John Wiley & Sons, Inc.
%V 12
%N 4
%P 636-43
%@ 1527-6465
%X This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Hing, A.
%A Hicks, M.
%A Gao, L.
%A Faddy, S.
%A Tran, P.
%A Kwan, J.
%A Kesteven, S.
%A Sharland, A.
%A Stewart, G.
%A Macdonald, P.
%T Hormone resuscitation of the brain dead donor and its effects on transplantable organs: Early results.
%B Immunology and Cell Biology
%D 2006
%C Australia
%I Blackwell Publishing Asia
%V 84
%N 3
%P A20-A20
%@ 0818-9641
%X 
%Z FOR Codes: 110708 110323


%0 Journal Article
%~ Isi
%A Lam, V.
%A Laurence, J.
%A Sharland, A.
%A McCaughan, G.
%A Hodgkinson, S.
%A Hall, B.
%A Allen, R.
%A Bishop, A.
%T Induction of long-term cardiac allograft survival using anti-lymphocyte antibodies in the rat model.
%B Immunology and Cell Biology
%D 2006
%C UK
%I Nature Publishing Group
%V 84
%N 3
%P A27-A27
%@ 0818-9641
%X 
%Z FOR Codes: 110708


%0 Journal Article
%~ Isi
%A Benseler, V.
%A Cordoba, S.
%A Wang, C.
%A Zvolynska, A.
%A Sharland, A.
%A Shlitt, H.
%A McCaughan, G.
%A Allen, R.
%A Bishop, G. A.
%T Microarray analysis of spontaneously tolerant compared to rejecting rat liver allografts.
%B Immunology and Cell Biology
%D 2006
%C UK
%I Nature Publishing Group
%V 84
%N 3
%P A31-A32
%@ 0818-9641
%X 
%Z FOR Codes: 110708


%0 Journal Article
%~ Isi
%A Laurence, J.
%A Wang, C. M.
%A Park, T.
%A Vis, A.
%A Allen, R. D. M.
%A Bishop, G. A.
%A Sharland, A. F.
%T Role of indoleamine dioxygenase (IDO) in rat models of transplantation rejection and tolerance.
%B Immunology and Cell Biology
%D 2006
%C UK
%I Nature Publishing Group
%V 84
%N 3
%P A30-A30
%@ 0818-9641
%X 
%Z FOR Codes: 110708


%0 Journal Article
%~ Isi
%A Wu, H. L.
%A Chen, G.
%A Wyburn, K.
%A Afifi, M.
%A Yin, J. L.
%A Eris, J.
%A Alexander, S.
%A Sharland, A.
%A Chadban, S.
%T TLR4 activation mediates kidney ischemia reperfusion injury.
%B Immunology and Cell Biology
%D 2006
%C Australia
%I Blackwell Publishing Asia
%V 84
%N 3
%P A29-A29
%@ 0818-9641
%X 
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Cordoba, S.
%A Wang, C.
%A Sharland, A.
%A McCaughan, G.
%A Allen, R.
%A Bishop, G. A.
%T Transcriptomics of tolerant and rejecting renal allografts.
%B Immunology and Cell Biology
%D 2006
%C UK
%I Nature Publishing Group
%V 84
%N 3
%P A2-A2
%@ 0818-9641
%X 
%Z FOR Codes: 110708