Cadaver Kidney Transplants

Karim

Kingsley³

et al. 2003

Transplantation

Section: "Random" Blood Transfusion Combined With Immunomodulation Gementioning

confidence: 99%

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect

Karim

Kingsley³

et al. 2003

Transplantation

“…While some patients were sensitized by pretransplant blood transfusions, others were not, and instead showed less rejection and improved graft survival compared with untransfused patients (Dossetor et al 1967;Morris et al 1968;Opelz et al 1973). As mentioned in ½ 1 the outcome of any immune response depends upon the context in which the antigen is recognized, the status of the recipient's immune system being a major factor.…”

Section: Alloantigen Pretreatmentmentioning

confidence: 99%

Alloantigen–induced specific immunological unresponsiveness

Wood

Jones

Phil. Trans. R. Soc. Lond. B

et al. 2001

When the immune system encounters alloantigen it can respond in any one of a number of di¡erent ways. The choice that is made will take into account factors such as where, when and how the contact with the alloantigen takes place, as well as the environmental conditions that prevail at the time the alloantigen is encountered. Alloantigen administration before transplantation either alone or in combination with therapeutic agents that modulate the functional activity of the responding leucocytes can be a powerful way of inducing speci¢c unresponsiveness to alloantigens in vivo. The molecular mechanisms that in£uence the way the outcome of the immune response to alloantigen develops, either activation or unresponsiveness to the triggering antigen, hold the key to our ability to manipulate the immune system e¡ectively by exposing it to donor antigen for therapeutic purposes. This review will focus on alloantigen-induced immunological unresponsiveness and how insights into the mechanisms of unresponsiveness have driven the development of novel tolerance-induction strategies that show promise for translation into the clinic in the future.

“…Reprogramming the immune system to induce specific unresponsiveness to alloantigens when it is already mature presents a much greater challenge, not least because of the presence of memory T cells in adults that can cross-react with donor alloantigens (11)(12)(13). Nevertheless, the administration of donor antigen, either alone or in combination with a variety of immunomodulating agents, to recipients of an allograft has been shown to result in improved graft survival in a variety of experimental and clinical situations (10,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). These observations highlight how powerful the administration of donor alloantigen can be, particularly in terms of promoting donor specific immunologic unresponsiveness that facilitates the survival of a subsequent allograft expressing one or more of the same alloantigens.…”

Section: Introductionmentioning

confidence: 99%

Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells

Wood

Jones

2011

Immunological Reviews

Exposure to alloantigen in vivo or in vitro induces alloantigen reactive regulatory T cells that can control transplant rejection. The mechanisms that underpin the activity of alloantigen reactive regulatory T cells in vivo are common with those of regulatory T cells that prevent autoimmunity. The identification and characterization of regulatory T cells that control rejection and contribute to the induction of immunologic unresponsiveness to alloantigens in vivo has opened up exciting opportunities for new therapies in transplantation. Findings from laboratory studies are informing the design of clinical protocols using regulatory T cells as a cellular therapy.