Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium.

Background: We investigated whether differentiation of embryonic stem cells (ESCs) in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection.

Methods And Results: In one series, 129/SvJ-derived mouse ESCs (ES-D3 line) were transplanted by direct myocardial injection (1 x 10(6) cells) into murine hearts of both allogeneic (BALB/c, n=20) and syngeneic (129/SvJ, n=12) recipients after left anterior artery ligation. Hearts were procured at 1, 2, 4, and 8 weeks after ESC transplantation and analyzed by immunohistochemistry to assess immune cell infiltration (CD3, CD4, CD8, B220, CD11c, Mac-1, and Gr-1) and ESC differentiation (hematoxylin and eosin).

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.

Progression of alloresponse and tissue-specific immunity during graft coronary artery disease.

Chronic rejection remains the major obstacle for long-term transplant survival. Both indirect alloresponse and tissue-specific autoimmunity have been implicated in its pathogenesis. The interrelationship between these two types of host anti-graft response remains poorly understood.

Graft coronary artery disease in murine cardiac allografts: proposal to meet the need for standardized assessment.

Background: Inconsistency exists in assessing the severity of graft coronary artery disease (GCAD) in studies that use mouse models. The central issue associated with this inconsistency is the lack of a standardized approach for assessing mouse GCAD.

Methods: We propose a new histologic definition of GCAD based on 3 successive stages (endotheliitis, premature lesion, and mature lesion) that mark the progression of this condition.

T-cell response to cardiac myosin persists in the absence of an alloimmune response in recipients with chronic cardiac allograft rejection.

Background: Immune-mediated injury to the graft has been implicated in the pathogenesis of chronic rejection. However, little is known regarding the nature of the antigen(s) involved in this immune process. We demonstrated that cardiac transplantation in mice induces an autoimmune T-cell response to a heart tissue-specific protein, cardiac myosin (CM).