Exhaustive depletion of graft resident dendritic cells: marginally delayed rejection but strong alteration of graft infiltration.
BACKGROUND
Donor dendritic cells (DDC) are believed to sustain direct recognition leading to acute allograft rejection. However, DDC are also required for tolerance induction in various models.


METHODS
We studied the effect of DDC depletion on major histocompatibility complex (MHC) mismatched rat heart allografts in a strain combination characterized by a DDC-dependant tolerance induction. Grafts were depleted of DDC either by pretreating donors with cyclophosphamide (CyP) or by being parked in an intermediate recipient treated with cyclosporine A (CsA).


RESULTS
CyP depleted 95% of resident DC and no specific donor MHC class II staining was observed in parked grafts. Parked grafts survived significantly but only moderately longer than untreated grafts (10.8+/-1.9 days vs. 6.5+/-0.5 days; P<0.05). Compared to unmodified grafts, on day 5 after transplantation, the magnitude of the graft infiltrate was dramatically decreased in DDC-depleted grafts, with IgG deposition within the grafts at the time of rejection. In parallel, the cytokine transcript levels were also lower in these grafts on day 5, but reached levels similar to those of unmodified grafts by day 7, indicating a delayed pattern of rejection.


CONCLUSIONS
Taken collectively, these data suggest that DDC depletion has a greater effect on the capacity of tolerance induction than the rejection process.
Roussey-Kesler
Gwenaëlle
G
Institut National de la Santé Et de la Recherche Médicale (INSERM) Unité 643, Immunointervention dans les Allo et xenotransplantations and Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France.
Brouard
Sophie
S
Ballet
Caroline
C
Moizant
Frederique
F
Moreau
Anne
A
Guillet
Marina
M
Smit
Helga
H
Usal
Claire
C
Soulillou
Jean-Paul
JP
D000208:Acute Disease; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D017209:Apoptosis; D003520:Cyclophosphamide / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000637:transplantation*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005802:Genes, MHC Class II / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D012313:RNA; D003520:Cyclophosphamide