Exhaustive Depletion of Graft Resident Dendritic Cells: Marginally Delayed Rejection but Strong Alteration of Graft Infiltration

Roussey-Kesler, Gwénaëlle; Brouard, Sophie; Ballet, Caroline; Moizant, Frédérique; Moreau, Anne; Guillet, Marina; Smit, Helga; Usal, Claire; Soulillou, Jean‐Paul

doi:10.1097/01.tp.0000168367.39204.07

Cited by 5 publications

(5 citation statements)

References 57 publications

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“…1W hearts depleted of resident DC are acutely rejected following the same tempo, indicating that the indirect pathway can rapidly develop in unmodified LEW. 1A hearts (29,30). The dominant peptides concerned the donor class II RT1.D u molecule sequence, in agreement with data obtained in different strain combinations (31)(32)(33).…”

Section: Discussionsupporting

confidence: 88%

“…To assess the cellular response in DST-treated recipients, we first needed to precisely characterize the dominant donor MHC peptides eliciting a T-cell response during acute rejection in unmodified LEW.1A recipients of MHC incompatible LEW.1W hearts. We measured the cellular response using the ELISPOT assay that enables (IgG1, IgG2a, IgG2b, IgG2c) Hematoxylin-eosin-saffron staining of heart allografts from 14,30,60 and 100) quantification of the frequency of T cells already committed to antigen. IFNc was chosen since it has been shown to offer the best correlation to rejection in various studies (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

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Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Ballet

Renaudin

Degauque

et al. 2009

American Journal of Transplantation

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Priming of recipients by DST induces long-term survival of mismatched allografts in adult rats. Despite these recipients developing inducible T regulatory cells able to transfer long-term graft survival to a secondary host, a state of chronic rejection is also observed. We revisited the molecular donor MHC targets of the cellular response in acute rejection and analyzed the cellular and humoral responses in recipients with long-term graft survival following transplantation. We found three immunodominant peptides, all derived from LEW.1W RT1.D u molecules to be involved in acute rejection of grafts from unmodified LEW.1A recipients. Although the direct pathway of allorecognition was reduced in DST-treated recipients, the early CD4 + indirect pathway response to dominant peptides was almost unimpaired. We also detected early and sustained antidonor class I and II antibody subtypes with diffuse C4d deposits on graft vessels. Finally, long-term accepted grafts displayed leukocyte infiltration, endarteritis and fibrosis, which evolved toward vascular narrowing at day 100. Altogether, these data suggest that the chronic graft lesions developed in long-term graft recipients are the result of progressive humoral injury associated with a persisting indirect T helper response. These features may represent a useful model for understanding and manipulating chronic active antibodymediated rejection in human.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Ballet

Renaudin

Degauque

et al. 2009

American Journal of Transplantation

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“…Moreover, the interaction of host CD4 ϩ cells with donor MHC class II molecules has been reported as critical for the rejection of murine cardiac allografts (15). However, in the same strain combination, removing DC from donor hearts (by irradiation or cyclophosphamide treatment) prolonged survival to a limited extent only (16). Thus, one can hypothesize that anti-donor MHC class II Abs could act in an active manner by inducing a regulatory signal after interaction with DC resident within the heart.…”

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confidence: 99%

Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells

Degauque

Lair

Dupont

et al. 2006

The Journal of Immunology

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Allograft acceptance can be induced in the rat by pretransplant infusion of donor blood or spleen cells. Although promoting long-term acceptance, this treatment is also associated with chronic rejection. In this study, we show that a single administration of anti-donor MHC class II alloimmune serum on the day of transplantation results in indefinite survival of a MHC-mismatched kidney graft. Long-term recipients accept a donor-type skin graft and display no histological evidence of chronic rejection. The kidney grafts of tolerant animals display an accumulation of TCR Cβ, FoxP3, and IDO transcripts. Moreover, as compared with syngeneic recipients, tolerant recipients harbor a large infiltrate of MHC class II+ cells and CD103+ cells. In vitro, splenocytes from tolerant recipients exhibit decreased donor-specific proliferation, which is restored by depletion of non-T cells and partially restored by the blockade of IDO. Finally, splenocytes from tolerant recipients, but not purified T cell splenocytes, transfer donor-specific infectious tolerance without chronic rejection, after infusion into naive recipients, over two generations. However, splenocytes depleted of T cells or splenocytes depleted of CD103+ cells fail to transfer tolerance. Collectively, these data show that a single administration of anti-donor MHC class II alloimmune serum induces a tolerant state characterized by an infiltration of the kidney graft by regulatory T cells and CD103+ cells. These data also show that the transfer of tolerance requires the presence of both T cells and CD103+ dendritic cells. The precise mechanism of cooperation of these two cell subsets remains to be defined.

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“…Practically speaking, our data demonstrate that patients with severe IR changes and low BDCA-1 þ cell density in postreperfusion biopsies are at increased risk of rejection and suggest that these patients may benefit from close clinical monitoring and/or modified immunosuppressive management. Finally, although our findings need to be confirmed in independent cohorts, our data provide a rationale to further investigate pretransplant-targeted therapies aimed at attenuating IRI 45 and/or eliminate donor DCs, 46 perhaps by donor pretreatment, to decrease early rejection episodes and thereby improve long-term allograft survival. Despite the unusually long CIT in our cohort, which may not be applicable to all transplant centers, taking appropriate measures in patients with severe IR changes and low DC density in their postreperfusion biopsies may help prevent overt or subclinical and/or smoldering rejection.…”

Section: Discussionmentioning

confidence: 69%

Analysis of dendritic cells and ischemia-reperfusion changes in postimplantation renal allograft biopsies may serve as predictors of subsequent rejection episodes

Batal

Mohan

Serres

et al. 2018

Kidney International

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Exhaustive Depletion of Graft Resident Dendritic Cells: Marginally Delayed Rejection but Strong Alteration of Graft Infiltration

Abstract: Taken collectively, these data suggest that DDC depletion has a greater effect on the capacity of tolerance induction than the rejection process.

Cited by 5 publications

References 57 publications

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Indirect CD4+ TH1 Response, Antidonor Antibodies and Diffuse C4d Graft Deposits in Long-Term Recipients Conditioned by Donor Antigens Priming

Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells

Analysis of dendritic cells and ischemia-reperfusion changes in postimplantation renal allograft biopsies may serve as predictors of subsequent rejection episodes

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