Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers

Bittencourt, Marcelo De Carvalho; Perruche, Sylvain; Contassot, Emmanuel; Fresnay, Stephanie; Baron, Marie‐Hélène; Angonin, R.; Aubin, F.; Hervé, P.; Tiberghien, Pierre; Saas, Philippe

doi:10.1182/blood.v98.1.224

Cited by 131 publications

(119 citation statements)

References 39 publications

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“…apoptotic leukocyte infusion to favor BM engraftment across MHC barriers. 31,35 We have previously shown that the apoptotic feature only and not the cell origin is implicated in favoring BM engraftment. 31 Here, we provide evidence that i.v.-infused apoptotic spleen cells were quickly captured by host splenic macrophages and DC.…”

Section: Discussionmentioning

confidence: 99%

“…31,35 We have previously shown that the apoptotic feature only and not the cell origin is implicated in favoring BM engraftment. 31 Here, we provide evidence that i.v.-infused apoptotic spleen cells were quickly captured by host splenic macrophages and DC. Donor phagocytes present in the BM graft were not implicated in the graft-facilitating effect of apoptotic spleen cell infusion.…”

Section: Discussionmentioning

confidence: 99%

“…infusion of apoptotic leukocytes to enhance bone marrow (BM) engraftment across major histocompatibility barriers, whatever their origin. 31 Here, we reported that after infusion, apoptotic spleen cells were engulfed by splenic DCs and macrophages. Depletion of donor phagocytes present in the graft had no effect on apoptotic cell-induced engraftment.…”

Section: Introductionmentioning

confidence: 92%

“…31,35 After isolation procedures, cell viability was always greater than 90% by Trypan Blue (Sigma) dye exclusion. Sca-1 þ cell-enriched grafts were obtained by immunomagnetic cell sorting (Miltenyi Biotec, Paris, France) from C57BL/ 6 BM cells according to the manufacturer's instructions.…”

Section: Cell Preparationmentioning

confidence: 99%

“…Splenocyte apoptosis was induced by a 40 Gy dose of g-irradiation 6 h before infusion to allow apoptotic changes to occur. 31 Apoptosis was confirmed by FITCconjugated Annexin-V (Beckman Coulter Immunotech, Marseille, France) and flow cytometry as well as Hoechst 33342 (Molecular Probes, Eugene, OR, USA) staining and UV microscopy. The absence of secondary necrosis was documented using Trypan Blue staining just before infusion.…”

Section: Cell Preparationmentioning

confidence: 99%

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Intravenous apoptotic spleen cell infusion induces a TGF-β-dependent regulatory T-cell expansion

et al. 2005

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Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-bdependent donor CD4 þ CD25 þ T-cell expansion. Such cells have a regulatory phenotype (CD62L high and intracellular CTLA-4 þ ), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

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Section: Discussionmentioning

confidence: 99%