CTLA-4-immunoglobulin and indoleamine 2,3-dioxygenase in dominant tolerance

  • Francesca Fallarino
  • Carmine Vacca
  • Claudia Volpi
  • Maria T. Pallotta
  • Stefania Gizzi
  • Ursula Grohmann
  • Paolo Puccetti
Part of the Progress in Inflammation Research book series (PIR)


The immune system is delicately balanced between self-antigen-driven tolerance and pathogen-driven immunity. In the healthy individual, these two states represent a sliding scale of responsiveness. A shift toward the extreme ends of this scale, i.e., lack of response or an excessive response (such as in autoimmunity and allergy) results in pathophysiological conditions that may be at the basis of diseases. As a consequence, several immune mechanisms have evolved to protect against T and B cells harboring the potential to recognize and become activated by self antigens. Establishment and regulation of self tolerance are exerted at two levels. First, the so-called “central tolerance”, which allows selection of T cells in the thymus (where the gene AIRE permits expression of tissue-specific genes), takes place during T cell development, and contributes to preventing maturation of autoreactive T lymphocytes [1]–[4]. In this process, the majority of self-reactive T cells are deleted by a mechanism termed “negative selection”, but at the same time, some CD4+ T cells differentiate to the CD4+CD25+Foxp3-expressing regulatory T cell (Treg) lineage [5]–[7]. The parameters specifying whether autoreactive CD4+ thymocytes are deleted (recessive tolerance) or differentiate into Tregs (dominant tolerance) remain unclarified.


Plasmacytoid Dendritic Cell Tryptophan Catabolism Tryptophan Catabolite Dominant Tolerance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Francesca Fallarino
    • 1
  • Carmine Vacca
    • 1
  • Claudia Volpi
    • 1
  • Maria T. Pallotta
    • 1
  • Stefania Gizzi
    • 1
  • Ursula Grohmann
    • 1
  • Paolo Puccetti
    • 1
  1. 1.Department of Experimental MedicineUniversity of PerugiaPerugiaItaly

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