Donor HO-1 Expression Inhibits Intimal Hyperplasia in Unmanipulated Graft Recipients: A Potential Role for CD8+ T-Cell Modulation by Carbon Monoxide

Abstract

Organs expressing cytoprotective HO-1 have a direct influence on the recipient immune response. Given the important role of CD8 T cells and IFN-gamma in chronic rejection, these data suggest that donor HO-1 expression may be useful to augment other immunosuppressive therapies to prolong graft survival and inhibit intimal hyperplasia.

Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

“…Briefly, the tissue was mashed through a 40-μm also been reported, which reduces rejection of organ transplants (81,82). In the present study, we showed that the generation of CD8 + CD122 + T cells with regulatory function was dependent on Hmox1 expression in mice.…”

Inhibition of Thrombin Receptor Signaling on α-Smooth Muscle Actin + CD34 + Progenitors Leads to Repair After Murine Immune Vascular Injury

“…10 Because this "single-hit" mechanical injury model has few clinical counterparts, we have continued this work using mouse aortas across a full major histocompatibility complex mismatch (H-2 d to H-2 b ) without immunosuppression, a model that involves rapid destruction of the endothelium of transplanted allografts and continuous immune-mediated damage to the donor vessel resulting in IH within 4 to 6 weeks. 12 …”

“…12 Briefly, a 5-mm segment of infrarenal donor aorta, flushed with heparin, was transplanted into recipient aorta. Blood flow was confirmed by direct inspection after the clamps were removed.…”

Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells

“…It is essential to determine whether restricting the expression of HO-1 exclusively to the transplanted organ can prevent graft rejection and thereby enhance the survival of the recipients. It has recently been reported that donor expression of HO-1 induced by hemin inhibited intimal hyperplasia of aorta in unmanipulated graft recipients by modulating CD8 þ cells [16]. However, in this study, the inducer was systemically administered, resulting in widespread but only transient expression of HO-1 in donors.…”

“…To date, the methods commonly employed to induce HO-1 expression cause widespread expression of HO-1 in the tissues of the transplant recipients [16]. It is essential to determine whether restricting the expression of HO-1 exclusively to the transplanted organ can prevent graft rejection and thereby enhance the survival of the recipients.…”