Induction of stable mixed chimerism by embryonic stem cells requires functional Fas/FasL engagement.
BACKGROUND
Recent data show the efficacy of embryonic stem cells (ESC) to engraft in allogeneic recipients without host pretreatment. This property is due to their low expression of major histocompatibility complex (MHC) class I antigens and lack of MHC class II expression. Here, we tested the hypothesis that the constitutive FasL expression by ESC is a requirement for their stable engraftment in allogeneic recipients.


METHODS
MRL and MRL-lpr/lpr mice (H-2k) were infused allogeneic 129SvJ RW-4 (H-2b) ESC without host preconditioning. The development of mixed chimerism was monitored over 100 days by flow cytometry.


RESULTS
Mixed chimerism was detectable by day 7. The amount of donor cells detected varied between 3-5.5% and were lymphoid, but nonmyeloid. Only 50% of lpr/lpr mice engrafted and lost donor cells by day 28 post-ESC infusion. In contrast, >80% wild type mice engrafted and maintained mixed chimerism up to day 100.


CONCLUSIONS
These data suggest a critical role for Fas-FasL engagement in ESC engraftment. We conclude that ESC may induce clonal deletion of alloreactive T cells by Fas-induced apoptosis in recipient T cells, protecting them from rejection. The data provide a rationale for improved protocols for the achievement of robust ESC-induced mixed chimerism.
Fabricius
Dorit
D
University of Iowa Hospitals and Clinics and VAMC Iowa City, Iowa City, Iowa 52242, USA.
Bonde
Sabrina
S
Zavazava
Nicholas
N
D000818:Animals; D002460:Cell Line; D053222:Fas Ligand Protein; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007519:Isoantigens; D008562:Membrane Glycoproteins; D019014:fas Receptor