Blockade of the PD-1/PD-1L pathway reverses the protective effect of anti-CD40L therapy in a rat to mouse concordant islet xenotransplantation model

Autor: Jiong Tian, Pablo Ramírez, Gang Mai, Maria-Luisa del Rio, Jose-Ignacio Rodriguez-Barbosa, Leo Buhler
Jazyk: angličtina
Rok vydání: 2007
Předmět:
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Clone (cell biology)
Islets of Langerhans Transplantation
Islets of Langerhans Transplantation/immunology/methods
B7-H1 Antigen
Rats
Sprague-Dawley
Mice
Cricetinae
Cricetulus/immunology
Transplantation
Heterologous/immunology/methods
Graft Survival/immunology
geography.geographical_feature_category
Membrane Glycoproteins
biology
ddc:617
Graft Survival
Antibodies
Monoclonal
Islet
CD40 Ligand/antagonists & inhibitors/immunology
Monoclonal
B7-1 Antigen
Peptides/antagonists & inhibitors/immunology
Antibody
Signal Transduction
medicine.drug_class
Xenotransplantation
Immunology
CD40 Ligand
Transplantation
Heterologous
Monoclonal antibody
Signal Transduction/drug effects/immunology
Diabetes Mellitus/chemically induced
Cricetulus
Antigens
CD274
Antigens
CD80/immunology
medicine
Diabetes Mellitus
Animals
Membrane Glycoproteins/antagonists & inhibitors/immunology
Transplantation
geography
Antigens
Differentiation/immunology
business.industry
Antigens
Differentiation
Blockade
Rats
Mice
Inbred C57BL
Disease Models
Animal
Cancer research
biology.protein
business
Peptides
Zdroj: Xenotransplantation, Vol. 14, No 3 (2007) pp. 243-8
ISSN: 0908-665X
Popis: We have previously demonstrated that costimulatory blockade with anti-CD40L monoclonal antibody (mAb) prolongs the survival of non-vascularized concordant rat to mouse islet xenografts. Here, we examine whether signaling through the PD-1/PD-1L pathway is required for the anti-CD40L therapy to prolong concordant islet graft survival using a novel anti-murine PD-1 mAb (clone 4F10).C57BL/6 mice received a cellular concordant islet xenograft under the left kidney capsule and four experimental groups were prepared. Group I: untreated control; group II: recipient mice were treated with three doses of 0.5 mg of anti-CD40L mAb (clone MR1) on days 0, 2 and 4; group III: mice were treated with 0.5 mg of anti-PD-1 (CD279) mAb (clone 4F10) every other day for 8 days; and finally group IV: mice received the combined treatment that consisted of anti-CD40L plus anti-PD-1 mAb.Concordant islet xenografts transplanted in control untreated mice showed a median survival time (MST) of 17 +/- 7.43 days, whereas anti-CD40L treatment led to a significant prolongation of graft survival (MST: 154 +/- 65.56, P0.0001). The administration of anti-PD-1 alone significantly accelerated graft rejection compared to non-treated controls (MST: 10 +/- 2.24 vs. MST: 17 +/- 7.43, P0.0004). Remarkably, the combined administration of anti-CD40L and anti-PD-1 reversed the protective effect obtained with anti-CD40L alone (anti-CD40L, MST: 154 +/- 65.56 vs. anti-CD40L plus anti-PD-1, MST: 10 +/- 7.72, P0.0002).Overall, our data indicate that the PD-1/PD-1L pathway is required for the achievement of prolonged graft survival in anti-CD40L-treated mice in a setting of rat to mouse concordant islet xenotransplantation.
Databáze: OpenAIRE
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