Intravenous infusion of apoptotic cells simultaneously with allogeneic hematopoietic grafts alters anti-donor humoral immune responses.
Intravenous infusion of apoptotic donor or third-party leukocytes simultaneously with an allogeneic donor bone marrow (BM) graft favors engraftment across major histocompatibility barriers. While verifying that such apoptotic cell infusion might not also be associated with antibody (Ab)-mediated allo-immune responses, we found, rather strikingly, that apoptotic cell infusion could in fact successfully prevent a humoral allo-immunization against a BM graft in mice. Indeed, among recipients having rejected their BM graft, prior apoptotic cell infusion was associated with a near absence of Ab-mediated allo-responses, while such an immunization was frequently observed in the absence of apoptotic cell infusion. This was also observed when infusing host apoptotic cells, thus showing that the prevention of immunization was linked to the apoptotic state of the cells rather than mediated by residual anti-recipient activity. In vivo anti-transforming growth factor-beta (TGF-beta) treatment resulted in the loss of this apoptotic cell infusion-associated protective effect on humoral allo-responses. Further studies will determine whether apoptotic cell infusion, in addition to hematopoietic graft facilitation might also contribute to preventing deleterious Ab-mediated allo-responses in various transplantation settings.
Unité mixte EFS/Université EA2284/Inserm U645, IFR 133, 25020 Besançon, France.
Sylvain
S
Perruche
François
F
Kleinclauss
Marcelo de Carvalho
Mde C
Bittencourt
Dominique
D
Paris
Pierre
P
Tiberghien
Philippe
P
Saas
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D005434:Flow Cytometry; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006413:Hematopoietic System / Q000502:physiology; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007262:Infusions, Intravenous / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous / Q000379:methods*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016212:Transforming Growth Factor beta