Engraftment of T-cell-depleted bone marrow in murine models for allogeneic bone marrow transplantation

Reisner, Yair

doi:10.1007/978-1-4613-1493-6_2

Cited by 6 publications

(1 citation statement)

References 23 publications

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“…This concept, of escalating stem cell doses to overcome rejection, was first successfully demonstrated in animal models in the early 90's. [16][17][18][19] In humans, escalation of the stem cell dose was afforded by the advent of granulocyte-colony stimulating factor (G-CSF) for donor CD34 + cell mobilization from the bone marrow (BM). 20 Thus, the goal of stem cell escalation was achieved in humans by supplementing the conventional T-cell-depleted bone marrow transplantation (TDBMT) with purified progenitors collected from the blood after administration of G-CSF to the donor.…”

Section: Crossing Hla Barriersmentioning

confidence: 99%

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

Or-Geva

Reisner

2015

Bone Marrow Transplant

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Allogeneic HSCT offers a route for achieving immune tolerance via mixed chimerism and remains the sole curative option for many nonmalignant, autoimmune and metabolic diseases. Present-day improvements of nonmyeloablative protocols are increasing the safety of HSCT, thereby widening the target population and resurrecting the interest of HSCT application as a platform for tolerance induction in organ transplantation. Using high cell doses of T-cell-depleted (TCD) grafts has been shown to circumvent graft-vs-host disease, leaving graft rejection as the main hindrance due to the robust host immunity that remains after mild conditioning. In this review we highlight the advantages of utilizing unique non-alloreactive 'veto' cells, such as anti-third party central memory CD8 T cells (Tcm), to enable induction of mixed chimerism after megadose HSCT under nonmyeloablative conditioning. Co-administration of HSCT with veto Tcm allows for induction of mixed chimerism that was successfully translated into immune tolerance, as demonstrated by engraftment of donor-type skin grafts. These veto Tcm cells have been shown to specifically eradicate anti-donor host T cells, through lymph-node sequestration and deletion, thus sparing host immunity and circumventing the need for life-long immunosuppression. Hence, data indicate that this treatment modality of combined TCD HSCT and adoptive transfer of Tcm veto cells under nonmyeloablative conditions may serve as a valuable tool for treatment of patients with a wide array of disorders such as hemoglobinopathies, autoimmune diseases and as a prelude for organ tolerance.

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Section: Crossing Hla Barriersmentioning

confidence: 99%

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

Or-Geva

Reisner

2015

Bone Marrow Transplant

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Prevention of lethal graft‐vs.‐host disease by a single low dose injection of anti‐T cell monoclonal antibody to the allograft recipients

1991

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We investigated the capacity of monoclonal antibody (mAb) treatment to prevent graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice, employing anti-T cell (subset) mAb and a fully allogeneic strain combination. In this strain combination, purified CD4+ cells were able to induce a lethal GVH reaction, whereas purified CD8+ cells were not. In the same strain combination, a single intraperitoneal injection of IgG2b anti-Thy-1 mAb, one day after reconstitution, caused a dose-dependent improvement of the survival. A single injection of a dose as low as 12.5 micrograms per mouse was already effective. Intravenous and intraperitoneal administration of the mAb appeared equally effective. For effective prevention of GVHD the treatment could be postponed until the 4th day after transplantation, but treatment delayed until day 6 was no longer effective. Treatment with IgG2b mAb specific for either helper or cytotoxic T cells also led to improvement of GVHD and survival, but was less effective than treatment with anti-Thy-1 mAb. Clinically, there was a difference in the effectiveness of anti-CD4 and anti-CD8 treatment, since symptoms of GVHD started earlier in the anti-CD8 treated group and the survival was better in the anti-CD4 treated group. These results press for prospective clinical studies employing anti-T cell mAb treatment early after allogeneic bone marrow transplantation, especially in HLA mismatched cases.

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Toward Safer CD34+ Megadose T-Cell-Depleted Transplants Following Reduced Intensity and Nonmyeloablative Conditioning Regimens

Or-Geva

Reisner

2017

Haploidentical Transplantation

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Engraftment of T-cell-depleted bone marrow in murine models for allogeneic bone marrow transplantation

Cited by 6 publications

References 23 publications

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

Prevention of lethal graft‐vs.‐host disease by a single low dose injection of anti‐T cell monoclonal antibody to the allograft recipients

Toward Safer CD34+ Megadose T-Cell-Depleted Transplants Following Reduced Intensity and Nonmyeloablative Conditioning Regimens

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