They are not stealthy in the heart: Embryonic stem cells trigger cell infiltration, humoral and T-lymphocyte-based host immune response

Objective: The in vivo immunogenicity of Embryonic Stem Cells is controversial. At present, there is only in vitro evidence of MHC I expression by this cell population but vivid speculation about their immune-privileged state. The immunology aspect of ESC transplantation deserves thorough investigation. Methods: We injected mouse ESC (expressing Green Fluorescent Protein, GFP) into injured myocardium of syngeneic, allogeneic and SCID recipients. Furthermore, we monitored host response for up to 4 weeks post cell transfer. We determined local response (CD 3, CD 11c expression by host cells), MHC I expression by donor cells, MHC-II expression within and around the graft, humoral response of allogeneic hosts using Flow Cytometry and evaluated the hosts' cytokine response using stimulated spleenocytes by means of ELISPOT. Cell survival was estimated by morphometry, by calculating the area of the GFP ⁺ graft over the area of infarction at multiple sections of the harvested heart. Results: There was significant cellular infiltration into and around the graft consisting of T-lymphocytes (CD3⁺) and dendritic cells (CD 11c). Infiltration was detectable at 1 week and progressed through 4 weeks following cell transplantation. The humoral Ab response was moderate at 2 weeks but frank at 4 weeks. ELISPOT demonstrated a Th1 pathway of donor specific T-lymphocyte response with strong IFN-γ and Il-2 production (figure A). MHC I expression was significant within the graft and maximal in the allogeneic groups. Conclusions: An immune response against transplanted ESC was demonstrated and the future use of ESC will likely require the use of systemic immunosuppression.