Interleukin-15 receptor blockade in non-human primate kidney transplantation.

Haustein, Silke

Kwun, Jean

Fechner, John

Kayaoglu, Ayhan

Faure, Jean-Pierre

Roenneburg, Drew

Torrealba, Jose

Knechtle, Stuart J

United States

2015-05-16T11:59:14Z

2010-04-27

BACKGROUND: Interleukin (IL)-15 is a chemotactic factor to T cells. It induces proliferation and promotes survival of activated T cells. IL-15 receptor blockade in mouse cardiac and islet allotransplant models has led to long-term engraftment and a regulatory T-cell environment. This study investigated the efficacy of IL-15 receptor blockade using Mut-IL-15/Fc in an outbred non-human primate model of renal allotransplantation. METHODS: Male cynomolgus macaque donor-recipient pairs were selected based on ABO typing, major histocompatibility complex class I typing, and carboxy-fluorescein diacetate succinimidyl ester-based mixed lymphocyte responses. Once animals were assigned to one of six treatment groups, they underwent renal transplantation and bilateral native nephrectomy. Serum creatinine level was monitored twice weekly and as indicated, and protocol biopsies were performed. Rejection was defined as a increase in serum creatinine to 1.5 mg/dL or higher and was confirmed histologically. Complete blood counts and flow cytometric analyses were performed periodically posttransplant; pharmacokinetic parameters of Mut-IL-15/Fc were assessed. RESULTS: Compared with control animals, Mut-IL-15/Fc-treated animals did not demonstrate increased graft survival despite adequate serum levels of Mut-IL-15/Fc. Flow cytometric analysis of white blood cell subgroups demonstrated a decrease in CD8 T-cell and natural killer cell numbers, although this did not reach statistical significance. Interestingly, two animals receiving Mut-IL-15/Fc developed infectious complications, but no infection was seen in control animals. Renal pathology varied widely. CONCLUSIONS: Peritransplant IL-15 receptor blockade does not prolong allograft survival in non-human primate renal transplantation; however, it reduces the number of CD8 T cells and natural killer cells in the peripheral blood.

http://www.ncbi.nlm.nih.gov/pubmed/20134394

1534-6080

https://hdl.handle.net/10161/10064

eng

Ovid Technologies (Wolters Kluwer Health)

Transplantation

10.1097/TP.0b013e3181d05a58

Animals

Antilymphocyte Serum

Biomarkers

Biopsy

CD8-Positive T-Lymphocytes

Creatinine

Drug Therapy, Combination

Flow Cytometry

Graft Rejection

Graft Survival

Humans

Immunoglobulin Fc Fragments

Immunosuppressive Agents

Kidney Transplantation

Killer Cells, Natural

Lymphocyte Count

Macaca fascicularis

Male

Mice

Models, Animal

Mycophenolic Acid

Receptors, Interleukin-15

Time Factors

Transplantation, Homologous

Interleukin-15 receptor blockade in non-human primate kidney transplantation.

Journal article

Kwun, Jean|0000-0002-8563-5472

Knechtle, Stuart J|0000-0002-1625-385X

http://www.ncbi.nlm.nih.gov/pubmed/20134394

937

944

8

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

School of Medicine

Surgery

Surgery, Abdominal Transplant Surgery

Published

89