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 β-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.