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, Jahrgang 35, 03.2016, S. 12-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -