Interfering With Contextual Fear Memories by Post-reactivation Administration of Propranolol in Mice: A Series of Null Findings.

Post-reactivation amnesia of contextual fear memories by blockade of noradrenergic signaling has been shown to have limited replicability in rodents. This is usually attributed to several boundary conditions that gate the destabilization of memory during its retrieval. How these boundary conditions can be overcome, and what neural mechanisms underlie post-reactivation changes in contextual fear memories remain largely unknown.

Zinc Concentration Dynamics Indicate Neurological Impairment Odds after Traumatic Spinal Cord Injury.

Traumatic Spinal Cord Injury (TSCI) is debilitating and often results in a loss of motor and sensory function caused by an interwoven set of pathological processes. Oxidative stress and inflammatory processes are amongst the critical factors in the secondary injury phase after TSCI. The essential trace element Zinc (Zn) plays a crucial role during this phase as part of the antioxidant defense system.

Anergic T cells actively suppress T cell responses via the antigen-presenting cell.

We here show that anergic T cells are active mediators of T cell suppression. In co-culture experiments, we found that anergic T cells, derived from established rat T cell clones and rendered anergic via T cell presentation of the specific antigen (Ag), were active inhibitors of T cell responses. Anergic T cells inhibited not only the responses of T cells with the same Ag specificity as the anergic T cells, but were also capable of efficiently inhibiting polyclonal T cell responses directed to other epitopes.

Specific tolerance induction and organ transplantation.

Induction of tolerance to histocompatibility antigens of an organ donor would eliminate the need for long-term administration of nonspecific immunosuppressive drugs associated with an increased risk of infection and malignancies. Recently, we established a murine model in which recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose of total body irradiation (TBI) and allogeneic bone marrow cells. Our results clearly demonstrate that stable multilineage mixed chimerism, immunocompetence and permanent donor-specific skin graft tolerance across full major histocompatibility (MHC) barriers can be successfully achieved in this way.

Haematopoietic stem cells can induce specific skin graft acceptance across full MHC barriers.

Previously, we and others have demonstrated in several animal models that the establishment of stable haematopoietic chimerism through allogeneic bone marrow transfusion provides an effective means for the development of specific transplantation tolerance. However, a major limitation to the clinical application of allogeneic bone marrow transfusion in immunosuppressed recipients for induction of tolerance to solid grafts, is the risk of graft-versus-host disease (GVHD). Therefore, it is important to identify the cell population needed for the induction of mixed chimerism and tolerance.

Specific tolerance induction and transplantation: a single-day protocol.

Bone marrow transfusion is a well-established method for induction of mixed hematopoietic chimerism and donor-specific tolerance in animal models. This procedure, however, is inapplicable in clinical transplantation using cadaveric donors due to the interval (1 week to 7 months) between tolerance induction and organ transplantation. For clinical use, it is essential that allografts be placed at the time of bone marrow transfusion.

A substantial level of mixed chimerism is required for the induction of permanent transplantation tolerance.

The induction of donor-specific transplantation tolerance is a major goal in organ transplantation, in order to eliminate the requirement for lifelong immunosuppressive therapy. Previously, we have developed a murine bone marrow transplantation model in which recipient mice were treated with a single dose of anti-CD3 and low dose whole body irradiation (WBI). Transfusion of donor bone marrow cells across a full H-2 disparity resulted in induction of high levels of stable mixed chimerism, specific T cell non-responsiveness and indefinite skin allograft survival.

Anti-CD3 treatment facilitates engraftment of full H-2-disparate donor bone marrow cells and subsequent skin allograft tolerance.

The aim of the present study was to induce engraftment of full H-2-disparate donor bone marrow cells and the development of subsequent transplantation tolerance. To this end, recipient H-2b mice were treated with anti-CD3 and on the same day received 6 Gy whole body irradiation as well as donor bone marrow cells (H-2d). Anti-CD3 treatment was chosen because it results in suppression of T cell function and in the release of CSF associated with enhancement of donor bone marrow engraftment.