Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection

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Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection. / Koch, Martina; Poehnert, Daniel; Nashan, Bjoern.

In: TRANSPL IMMUNOL, Vol. 35, 03.2016, p. 12-7.

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@article{663d97c18f1c4a32928889701917b857,
title = "Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection",
abstract = "AIMS: Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection.METHODS: LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells. In the intervention group (n=7) FTY720 therapy was started 7 weeks post-KTx in a dose of 0.5 mg/kg p. o. three times a week.RESULTS: In the control group the survival of the rats was 9, 11, 18 and 4 × 24 weeks, in the intervention group 2 × 8, 9, 2 × 11, 18 and 20 weeks. While in the intervention group the number of T- and B-lymphocytes in the peripheral blood was successfully reduced during FTY720 treatment, both groups showed significant amounts of T- and B-lymphocytes in the kidney grafts. Animals in both groups developed donor specific antibodies, extensive albuminuria and severe chronic changes in the grafts.CONCLUSIONS: FTY720 was highly effective to reduce T- and B-lymphocytes in the peripheral blood, but not effective in clearing their infiltration in the graft. Graft survival was not prolonged by FTY720 treatment starting late after kidney transplantation.",
keywords = "Animals, B-Lymphocytes, Chronic Disease, Disease Models, Animal, Fingolimod Hydrochloride, Graft Rejection, Immunity, Cellular, Immunity, Humoral, Kidney Transplantation, Rats, T-Lymphocytes, Journal Article, Research Support, Non-U.S. Gov't",
author = "Martina Koch and Daniel Poehnert and Bjoern Nashan",
note = "Copyright {\textcopyright} 2016 Elsevier B.V. All rights reserved.",
year = "2016",
month = mar,
doi = "10.1016/j.trim.2016.01.003",
language = "English",
volume = "35",
pages = "12--7",
journal = "TRANSPL IMMUNOL",
issn = "0966-3274",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection

AU - Koch, Martina

AU - Poehnert, Daniel

AU - Nashan, Bjoern

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/3

Y1 - 2016/3

N2 - AIMS: Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection.METHODS: LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells. In the intervention group (n=7) FTY720 therapy was started 7 weeks post-KTx in a dose of 0.5 mg/kg p. o. three times a week.RESULTS: In the control group the survival of the rats was 9, 11, 18 and 4 × 24 weeks, in the intervention group 2 × 8, 9, 2 × 11, 18 and 20 weeks. While in the intervention group the number of T- and B-lymphocytes in the peripheral blood was successfully reduced during FTY720 treatment, both groups showed significant amounts of T- and B-lymphocytes in the kidney grafts. Animals in both groups developed donor specific antibodies, extensive albuminuria and severe chronic changes in the grafts.CONCLUSIONS: FTY720 was highly effective to reduce T- and B-lymphocytes in the peripheral blood, but not effective in clearing their infiltration in the graft. Graft survival was not prolonged by FTY720 treatment starting late after kidney transplantation.

AB - AIMS: Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection.METHODS: LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells. In the intervention group (n=7) FTY720 therapy was started 7 weeks post-KTx in a dose of 0.5 mg/kg p. o. three times a week.RESULTS: In the control group the survival of the rats was 9, 11, 18 and 4 × 24 weeks, in the intervention group 2 × 8, 9, 2 × 11, 18 and 20 weeks. While in the intervention group the number of T- and B-lymphocytes in the peripheral blood was successfully reduced during FTY720 treatment, both groups showed significant amounts of T- and B-lymphocytes in the kidney grafts. Animals in both groups developed donor specific antibodies, extensive albuminuria and severe chronic changes in the grafts.CONCLUSIONS: FTY720 was highly effective to reduce T- and B-lymphocytes in the peripheral blood, but not effective in clearing their infiltration in the graft. Graft survival was not prolonged by FTY720 treatment starting late after kidney transplantation.

KW - Animals

KW - B-Lymphocytes

KW - Chronic Disease

KW - Disease Models, Animal

KW - Fingolimod Hydrochloride

KW - Graft Rejection

KW - Immunity, Cellular

KW - Immunity, Humoral

KW - Kidney Transplantation

KW - Rats

KW - T-Lymphocytes

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.trim.2016.01.003

DO - 10.1016/j.trim.2016.01.003

M3 - SCORING: Journal article

C2 - 26802360

VL - 35

SP - 12

EP - 17

JO - TRANSPL IMMUNOL

JF - TRANSPL IMMUNOL

SN - 0966-3274

ER -