Embryonic stem cells and their differentiated derivatives have a fragile immune privilege but still represent novel targets of immune attack.
Embryonic stem cells (ESCs) offer an attractive potential in cell replacement therapy and regenerative medicine because of their inherent plasticity and ability to self-renew. However, the immunological response against transplanted ESC-derived allografts requires further evaluation. In this study, we showed that ESCs expressing the major histocompatibility complex class I molecule H2K(b) escape immune recognition by H2K(b)-reactive CD8(+) T cells, irrespective of H2K(b) expression levels. In the face of more robust immunological challenge, however, evidence of ESC allograft rejection becomes apparent. We further assessed the adaptive immune response against terminally differentiated insulin-producing tissue derived from an ESC source to examine the potential future applicability of this tissue as a beta-cell replacement therapy for type 1 diabetes mellitus. The functional ESC-derived insulin-producing tissue was infiltrated by alloreactive T cells and rejected in immunocompetent hosts. Hence, although ESCs and their terminally differentiated derivatives may possess a fragile immune privilege, they still represent novel targets of attack by elements of the immune system and are rejected. These findings provide insight into the mechanisms of adaptive immunity toward ESCs and their derivatives. Disclosure of potential conflicts of interest is found at the end of this article.
Transplantation Research Immunology Group, Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. kathryn.wood@nds.ox.ac.uk
Douglas C
DC
Wu
Ashleigh Susan
AS
Boyd
Kathryn J
KJ
Wood
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000276:immunology*; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000276:immunology*; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014184:Transplantation, Homologous
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007371:Interferon-gamma