Clinical tolerance in allogeneic hematopoietic stem cell transplantation

Maria Grazia Roncarolo, Silvia Gregori, Barbarella Lucarelli, Fabio Ciceri, Rosa Bacchetta

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)145-163
Number of pages19
JournalImmunological Reviews
Volume241
Issue number1
DOIs
Publication statusPublished - May 2011

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Immunological tolerance
  • Interleukin-10
  • Ntreg cells
  • Regulatory T cells
  • Tr1 cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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