Dendritic cells, tolerance and therapy of organ allograft rejection

Giorgio Raimondi, Angus W. Thomson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Donor dendritic cells (DCs) and those of host origin play key roles in the instigation and maintenance of immune responses to organ allografts. In the normal steady state, however, DCs are important for the maintenance of central and peripheral tolerance. Moreover, the presence of those cells in donor hematopoietic cell infusions may facilitate the induction of transplant tolerance. Accrual of information regarding DC tolerogenicity has driven the assessment of DC-based therapy of allograft rejection. Pioneering work demonstrating increased allograft survival after pretransplant infusion of immature donor-derived DC has prompted the evaluation of several approaches to the generation of DCs with tolerogenic/regulatory properties. These include: identification of specific culture conditions for propagation of homogenous populations of immature DCs; pharmacological manipulation of DCs to stabilize their immature/tolerogenic phenotype; and genetic modification of DCs to impair their stimulating ability/enhance their tolerogenicity. These approaches have rendered DCs capable of markedly prolonging experimental allograft (including kidney transplant) survival and promoting donor-specific tolerance. Recently identified molecular signaling pathways that play key roles in the outcome of DC-T cell interaction are likely to become novel targets for manipulation of allograft immunity and for the promotion of transplant tolerance.

Original languageEnglish (US)
Title of host publicationKidney Transplantation
Subtitle of host publicationStrategies to Prevent Organ Rejection
EditorsC. Ronco, S. Chiaramonte, G. Remuzzi
Pages105-120
Number of pages16
StatePublished - 2005
Externally publishedYes

Publication series

NameContributions to Nephrology
Volume146
ISSN (Print)0302-5144

ASJC Scopus subject areas

  • Nephrology

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