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Intragraft CD11b+IDO+ Cells Mediate Cardiac Allograft Tolerance by ECDI‐Fixed Donor Splenocyte Infusions

Chen, G. ; Kheradmand, T. ; Bryant, J. ; Wang, S. ; Tasch, J. ; Wang, J.‐j. ; Zhang, Z. ; Luo, X.

American journal of transplantation, 2012-11, Vol.12 (11), p.2920-2929 [Periódico revisado por pares]

Malden, USA: Blackwell Publishing Inc

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Título:
Intragraft CD11b+IDO+ Cells Mediate Cardiac Allograft Tolerance by ECDI‐Fixed Donor Splenocyte Infusions
Autor: Chen, G. ; Kheradmand, T. ; Bryant, J. ; Wang, S. ; Tasch, J. ; Wang, J.‐j. ; Zhang, Z. ; Luo, X.
Assuntos: 3 dioxygenase ; Analysis of Variance ; Animals ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antigen-Presenting Cells - drug effects ; Antigen-Presenting Cells - immunology ; Antigen-Presenting Cells - pathology ; Biological and medical sciences ; Cardiac transplantation ; CD11b Antigen - drug effects ; CD11b Antigen - immunology ; Cell Transplantation ; Cytokines ; Disease Models, Animal ; ECDI (ethylene carbodiimide) ; Fluorescent Antibody Technique ; Foxp3+ regulatory T cells ; Gr1+ monocytes ; Graft Rejection - prevention & control ; Graft Survival ; Heart Transplantation - adverse effects ; Heart Transplantation - methods ; IDO (indoleamine 2 ; IL‐10 (interleukin 10) ; IL‐13 (interleukin 13) ; Immunohistochemistry ; Indoleamine-Pyrrole 2,3,-Dioxygenase - drug effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Isoantigens - administration & dosage ; Isoantigens - immunology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Pharmacology. Drug treatments ; Random Allocation ; rapamycin ; Sirolimus - pharmacology ; Spleen - cytology ; Statistics, Nonparametric ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; tolerance ; Transplantation Tolerance - drug effects ; Transplantation Tolerance - immunology ; Transplantation, Homologous ; Transplants & implants
É parte de: American journal of transplantation, 2012-11, Vol.12 (11), p.2920-2929
Notas: These authors contributed equally.
Co‐senior authors.
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Descrição: We have previously shown that pre‐ and post‐transplant infusions of donor splenocytes treated with 1‐ethyl‐3‐(3’‐dimethylaminopropyl)‐carbodiimide (ECDI‐SPs) provide permanent donor‐specific protection of islet allografts. The efficacy of donor ECDI‐SPs in protecting vascularized cardiac allografts and mechanism(s) of protection are unknown. In this study, we show that infusions of ECDI‐SPs significantly prolong cardiac allograft survival concomitant with an impressive accumulation of CD11b+IDO+ cells in the cardiac allograft, and that the presence of this population is dependent on Gr1+ cells. Consequently, depletion of Gr1+ cells or inhibition of indoleamine 2,3 dioxygenase (IDO) activity abrogates graft protection by ECDI‐SPs infusions. In addition, T cells from ECDI‐SPs treated recipients secrete high levels of interleukin 10 and interleukin 13 upon in vitro restimulation, which are also dampened in recipients treated with the IDO inhibitor. Furthermore, combination of donor ECDI‐SPs with a short course of rapamycin provides indefinite cardiac allograft survival in 100% of the recipients. These findings reveal a novel mechanism of donor ECDI‐SPs in inducing cardiac transplant tolerance and provide several targets that are amenable to therapeutic manipulations for tolerance induction for cardiac transplantation. Cardiac transplantation tolerance induced by infusion of ECDI‐treated donor splenocytes is dependent on Gr1+ and CD11b+IDO+ cell populations, concomitant with increased presence of intragraft regulatory T cells and increased T cell production of IL‐10 and IL‐13.
Editor: Malden, USA: Blackwell Publishing Inc
Idioma: Inglês

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Intragraft CD11b+IDO+ Cells Mediate Cardiac Allograft Tolerance by ECDI‐Fixed Donor Splenocyte Infusions

Chen, G. ; Kheradmand, T. ; Bryant, J. ; Wang, S. ; Tasch, J. ; Wang, J.‐j. ; Zhang, Z. ; Luo, X.

Malden, USA: Blackwell Publishing Inc

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