Abstract:
BACKGROUND:The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes (MHCs) are critical discrepancies. Here, we established a rat model of chronic rejection using fully MHC-mismatched strains in which kidney disease progresses even under immunosuppressive therapy. METHODS:LEW (RT1(l)) rats were used as donors and Brown Norway (BN, RT1(n)) rats as recipients. Intramuscular administration of 0.1mg/kg of tacrolimus was initiated on the day of transplantation. Post-transplantation, this dose was maintained until Day 9, suspended until Day 28 and then resumed from Day 29. Renal function, histopathology, and levels of donor-specific antibody (DSA) and several biomarkers of renal injury were assessed. RESULTS:On Day 91 post-transplantation, recipients received tacrolimus treatment with short-term suspension exhibited reduced renal function and changes in histology. Those were characteristics of chronic rejection including glomerulosclerosis, interstitial fibrosis, and tubular atrophy in human transplantation recipients. Urinary protein excretion increased in a linear fashion, and elevated levels of several biomarkers of renal injury and DSA were observed even under administration of an immunosuppressant. CONCLUSIONS:We established an allograft rejection model with impaired renal function and typical histopathological changes of chronic rejection in fully MHC-mismatched rats by controlling administration of an immunosuppressant. These findings suggest that this model more accurately reflects transplantation in a clinical setting than existing models and enables the evaluation of therapeutic agents.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Hanaoka K,Kawato Y,Kubo K,Nakanishi T,Maeda M,Nakamura K,Hirose J,Noto T,Fukahori H,Fujikawa A,Miyoshi S,Takakura S,Morokata T,Higashi Ydoi
10.1016/j.trim.2016.08.002subject
Has Abstractpub_date
2016-09-01 00:00:00pages
19-26eissn
0966-3274issn
1878-5492pii
S0966-3274(16)30078-8journal_volume
38pub_type
杂志文章abstract::We have developed a highly sensitive method for the simultaneous crossmatching of T and B cells using three-colour flow cytometry. This method identifies T and B cell populations in a lymphocyte sample and analyses each for the presence of bound patient IgG alloantibodies. A fluorescein isothiocyanate conjugated rabbi...
journal_title:Transplant immunology
pub_type: 杂志文章
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journal_title:Transplant immunology
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doi:10.1016/j.trim.2007.03.003
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pub_type: 杂志文章,随机对照试验
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更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. METHODS:Core bi...
journal_title:Transplant immunology
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abstract::Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglob...
journal_title:Transplant immunology
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journal_title:Transplant immunology
pub_type: 杂志文章,评审
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更新日期:2002-08-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.03.002
更新日期:2009-07-01 00:00:00
abstract::It is known that the expression level of the heat shock protein (HSP) is elevated in allograft tissues, but the specific role of the HSP in the acute rejection has not been elucidated. This study aims to determine how and when the HSP72 molecule works immunologically in the process of acute allograft rejection from a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2004.08.003
更新日期:2004-12-01 00:00:00
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journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/j.trim.2013.08.002
更新日期:2013-12-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.01.003
更新日期:2016-03-01 00:00:00
abstract:INTRODUCTION:Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3 express...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.06.011
更新日期:2010-10-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80001-x
更新日期:1999-12-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.07.002
更新日期:2005-12-01 00:00:00
abstract::The aetiologies of accelerated or transplant-associated coronary artery disease (TxCAD) following cardiac transplantation and chronic rejection following renal transplantation remain ill-defined. Previous studies have used Western blotting to demonstrate an association between the formation of anti-endothelial (anti-E...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(97)80021-4
更新日期:1997-03-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.09.007
更新日期:2010-02-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80026-4
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更新日期:2014-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.trim.2012.04.002
更新日期:2012-08-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
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更新日期:1994-09-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
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journal_title:Transplant immunology
pub_type: 杂志文章
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更新日期:2008-05-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章,评审
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更新日期:2005-08-01 00:00:00
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journal_title:Transplant immunology
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journal_title:Transplant immunology
pub_type: 杂志文章
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更新日期:2017-02-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2006.09.022
更新日期:2006-12-01 00:00:00
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journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.027
更新日期:2006-11-01 00:00:00