Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Background: Extracorporeal Photopheresis (ECP) is an immune therapy in which blood leukocytes are treated with 8-methoxypsoralen (8-MOP), exposed to UV-A light, and re-infused. This study aims to determine whether treatment of donor splenocytes (DSP) with ECP (ECP-DSP) prior to transplant facilitates induction of donor specific tolerance. Methods: DSP from BALB/c mice were isolated and treated with ECP. ECP-DSP were infused I.V. into full MHC mismatched B6 mice (allografts) 7 days prior to heterotopic heart transplant (n=10) with or without short course Rapamycin (RAPA). Abdominal palpation of donor heart beat was used to assess graft survival; rejection was defined as loss of palpable cardiac impulse. Untreated allograft and isograft served as controls. Specificity was tested by transplanting heart allografts from unrelated donor mice (C3H). Additional transplants were sacrificed at pre-designated times for histological and phenotypical analyses. Results: Recipients treated with a single infusion of ECP-DSP had significantly longer allograft survival (median survival time (MST)=21 days) compared to untreated allografts (MST=7 days, p<0.01). Combining ECP-DSP with short course RAPA (0.5mg/kg, I.P.) further extended allograft survival to a MST of 59 days compared to RAPA alone (MST=27days). Graft protection was donor specific as recipients receiving ECP-DSP from BALB/c mice rejected C3H cardiac allografts similar to untreated controls. Inflammatory cell infiltrates (CD3, gr-1, CD11b) were markedly reduced in ECP-DSP treated allografts, compared to untreated controls, on post-operative day 7 by histology and immunohistochemistry. Numbers of CD44hiCD62Llow effector T cells (CD4 and CD8) and IFN-γ producing CD4 and CD8 T-cells were also decreased in the spleens from ECP-DSP group. Production of donor specific antibodies (DSA) was significantly reduced in the ESP-DSP group (p<0.05, vs controls). Conclusions: Preconditioning with a single infusion of ECP-DSP inhibits T cell priming, effector T cell differentiation, and DSA production, resulting in significantly prolonged cardiac allograft survival. Pre-emptive infusion of ECP-DSP has significant potential for clinical translation for living donor transplants.
To cite this abstract in AMA style:Schneiderman J, Ye J, Yeap X, Caralt M, Wang J-J, Zhang Z. Single Infusion of Donor-Type Splenocytes Treated With Extracorporeal Photopheresis Prior to Transplantation Significantly Prolongs Cardiac Allograft Survival in Mice [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/single-infusion-of-donor-type-splenocytes-treated-with-extracorporeal-photopheresis-prior-to-transplantation-significantly-prolongs-cardiac-allograft-survival-in-mice/. Accessed May 27, 2020.
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