The immunology of chronic allograft injury

Raphael Thuillier, Roslyn B. Mannon

Research output: Chapter in Book/Report/Conference proceedingChapter


The causcs of chronic graft injury are diverse and are dependant on the recipient, donor organ and immunosuppressive strategy. In this chapter, we explore the contribution of the immune system to this problem, recognizing that nonimmune factors have been shown to contribute to chronic injury as well. An immune response commences with the recognition of foreign antigen (allorecognition), which can occur by one of two pathways: direct and indirect. Although it is reported that the direct pathway has a role to play in the etiology of chronic graft injury, the indirect pathway is believed be a primary participant and a process that may not be specifically affected by immunosuppression. Once activated, requiring costimulatory signals, T'Cells mediate a signaling cascade that will alter the milieu of the graft and activate other participants of the immune response. Not only are CD4+ and CD8+ T-cells participate, but monocytes, eosinophils and mast cells may also contribute to late graft injury. Blockade of this allorecognition process as well as blocking T-cell costimulation may ameliorate chronic graft injury. Moreover, activated CD4+ T-cells also have the capability to induce clonal differentiation of B-cells, resulting in alloantibody production—another critical mechanism of immune-mediated injury. In this chapter, we will review the mechanisms of immune cell activation and allorecognition, explore the role of both cellular and antibody mediated immune responses in chronic graft injury and explore the outcome of therapeutic intervention. The contribution of viral infection and its immune response within the graft will also be discussed. By understanding the immune mechanisms of chronic graft injury, we can further identify new markers and strategies to limit this injury in our recipients.

Original languageEnglish (US)
Title of host publicationChronic Allograft Failure
Subtitle of host publicationNatural History, Pathogenesis, Diagnosis and Management
PublisherCRC Press
Number of pages10
ISBN (Electronic)9781498712729
ISBN (Print)9781587061530
StatePublished - Jan 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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