Cyclosporine A but Not Corticosteroids Support Efficacy of Expanded, Adoptively Transferred Human Tregs in GvHD.

Reshaping the immune balance by adoptive transfer of regulatory T-cells (Tregs) has emerged as a promising strategy to combat undesired immune reactions, including in Graft-versus-Host Disease (GvHD), which is the most lethal non-relapse complication of allogeneic hematopoietic stem cell transplantation. Currently however, little is known about the potentially inhibitory effects of conventional immunosuppressive drugs, which are routinely used to treat GvHD, on adoptively transferred Tregs. Here we demonstrate drug-specific effects of the conventional immunosuppressive drugs Cyclosporine A, Mycophenolate mofetil and methylprednisolone on adoptively transferred Tregs in a humanized NOD/SCID/IL2Rgamma-/- GvHD mouse model.

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival.

Purpose: To analyze the immune modulatory effect of low-dose systemic treatment with rapamycin (Rapa) alone or in combination with cyclosporin A (CsA) in a high-responder corneal allograft model.

Methods: A total of 80 C57BL/6 mice received corneal grafts from BALB/c donors. Recipients were treated with either CsA 3 mg/kg/day or Rapa 0.

CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells.

Human natural killer (NK) cells comprise 2 main subsets, CD56(bright) and CD56(dim) cells, that differ in function, phenotype, and tissue localization. To further dissect the heterogeneity of CD56(dim) cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK-cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56(dim) CD62L(+) cells.

A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy.

T-bet plays a crucial role in Th1 development. We investigated the role of T-bet in the development of allograft rejection in an established MHC class II-mismatched (bm12 into B6) model of chronic allograft vasculopathy (CAV). Intriguingly, and in contrast to IFN-gamma(-/-) mice that are protected from CAV, T-bet(-/-) recipients develop markedly accelerated allograft rejection accompanied by early severe vascular inflammation and vasculopathy, and infiltration by predominantly IL-17-producing CD4 T cells.

Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3.

The induction of heme oxygenase 1 (HO-1) by a single treatment with cobalt protoporphyrin (CoPPIX) protects against inflammatory liver failure and ischemia reperfusion injury after allotransplantation. In this context, the HO-1-mediated inhibition of donor-derived dendritic cell maturation and migration is discussed as one of the key events of graft protection. To investigate the poorly understood mechanism of CoPPIX-induced HO-1 activity in more detail, we performed gene expression analysis in murine liver, revealing the up-regulation of STAT3 after CoPPIX treatment.

Modulation of graft arteriosclerosis in a rat carotid transplantation model.

Background: Venous autografts used in cardiovascular surgery tend to deteriorate over time due to arteriosclerotic complications. Cadaveric vascular allografts represent a possible alternative for this application, but donor endothelial cells (ECs) and antigen presenting cells of the graft trigger alloresponses mediated by MHC class I (MHC I) antigen, leading to graft failure. Vascular allograft rejection might be prevented by reducing cell surface expression of MHC I and thereby lowering the immunogenicity of the grafts.

Orthotopic heart transplantation in patients with Marfan syndrome.

Background: Due to the risk of vascular complications, the indication for heart transplantation (HTx) in patients with Marfan syndrome and end-stage heart disease remains controversial. We analyzed the results of such patients who underwent HTx at our institution.

Methods: Ten patients with Marfan syndrome (median age 36, range 19 to 56 years) underwent HTx between March 1986 and December 2005.