Abstract

The aim of this study was to test the hypothesis that CTLA4-Ig will prolong survival of renal allografts in a nonhuman primate model. CTLA4-Ig has been shown to modify the allograft rejection response to produce prolonged graft survival and/or induce specific unresponsiveness in rodent models. Adult rhesus macaques (11.8-13.5 kg) were utilized for these studies. Ten animals received an allogeneic renal transplant, a left nephrectomy and simultaneous right contralateral ureter ligation. The paired transplants were performed simultaneously by exchange of kidneys between recipient individuals. One recipient in each pair was treated with CTLA4-Ig and the other served as a control being treated with human albumin. Renal allografts in the control treatment group promptly fail (4-8 days) and the histologic analysis suggests both a cellular and humoral immune mediated mechanism. CTLA4-Ig treatment in one of four recipients was associated with marked prolongation of allograft su rvival. One CTLA4-Ig treated recipient died secondary to necrosis of the distal transplant ureter and was not included in the analysis. In summary, the results of this pilot study suggest that CTLA4-Ig has the ability to prolong primate renal allograft survival.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
3P51RR000165-37S1
Application #
2711853
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

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Li, Chun-Xia; Kempf, Doty J; Tong, Frank C et al. (2018) Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures. Comp Med :
Lacreuse, Agnès; Parr, Lisa; Chennareddi, Lakshmi et al. (2018) Age-related decline in cognitive flexibility in female chimpanzees. Neurobiol Aging 72:83-88
Meng, Yuguang; Hu, Xiaoping; Zhang, Xiaodong et al. (2018) Diffusion tensor imaging reveals microstructural alterations in corpus callosum and associated transcallosal fiber tracts in adult macaques with neonatal hippocampal lesions. Hippocampus 28:838-845
Mylvaganam, Geetha H; Chea, Lynette S; Tharp, Gregory K et al. (2018) Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV. JCI Insight 3:
Kamara, Dennis M; Gangishetti, Umesh; Gearing, Marla et al. (2018) Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer's Disease. J Alzheimers Dis 62:1815-1826
Ploquin, Mickaël J; Casrouge, Armanda; Madec, Yoann et al. (2018) Systemic DPP4 activity is reduced during primary HIV-1 infection and is associated with intestinal RORC+ CD4+ cell levels: a surrogate marker candidate of HIV-induced intestinal damage. J Int AIDS Soc 21:e25144
Fonseca, Jairo A; McCaffery, Jessica N; Caceres, Juan et al. (2018) Inclusion of the murine IgG? signal peptide increases the cellular immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage vaccine. Vaccine 36:2799-2808
Tedesco, Dana; Thapa, Manoj; Chin, Chui Yoke et al. (2018) Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic ?? T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease. Gastroenterology 154:2178-2193
Robinson, Amy A; Abraham, Carmela R; Rosene, Douglas L (2018) Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience 40:31-47

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