Clinical tolerance in allogeneic hematopoietic stem cell transplantation

Authors

  • Maria-Grazia Roncarolo,

    1. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells, Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
    2. Vita-Salute San Raffaele University, Milan, Italy.
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  • Silvia Gregori,

    1. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells, Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
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  • Barbarella Lucarelli,

    1. Department of Paediatric Haematology-Oncology, IRCCS Ospedale Bambino Gesù, Rome, Italy.
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  • Fabio Ciceri,

    1. Hematology and BMT Unit, San Raffaele Hospital, Milan, Italy.
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  • Rosa Bacchetta

    1. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells, Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
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Maria-Grazia Roncarolo
HSR-TIGET, Via Olgettina 58, 20132 Milan, Italy
Tel.: +39 02 2643 4875
Fax: +39 02 2643 4668
e-mail: m.roncarolo@hsr.it

Abstract

Summary:  Allogeneic hematopoietic stem cell transplantation (HSCT) has been a curative therapeutic option for a wide range of immune hematologic malignant and non-malignant disorders including genetic diseases and inborn errors. Once in the host, allogeneic transplanted cells have not only to ensure myeloid repopulation and immunological reconstitution but also to acquire tolerance to host human leukocyte antigens via central or peripheral mechanisms. Peripheral tolerance after allogeneic HSCT depends on several regulatory mechanisms aimed at blocking alloimmune reactivity while preserving immune responses to pathogens and tumor antigens. Patients transplanted with HSCT represent an ideal model system in humans to identify and characterize the key cellular and molecular players underlying these mechanisms. The knowledge gained from these studies has allowed the development of novel therapeutic strategies aimed at inducing long-term peripheral tolerance, which can be applicable not only in allogeneic HSCT but also in autoimmune diseases and solid-organ transplantation. In the present review, we describe Type 1 regulatory T cells, initially discovered and characterized in chimeric patients transplanted with human leukocyte antigen-mismatched HSCT, and how their presence correlates to tolerance induction and maintenance. Furthermore, we summarize different cell therapy approaches with regulatory T cells, designed to facilitate tolerance induction, minimizing pharmaceutical interventions.

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