Making regulatory T cells with defined antigen specificity: Role in autoimmunity and cancer

Karsten Kretschmer, Irina Apostolou, Elmar Jaeckel, Khashayarsha Khazaie, Harald Von Boehmer

Research output: Contribution to journalReview article

80 Scopus citations

Abstract

There is increasing evidence that agonist ligand presentation either intrathymically or extrathymically plays a crucial if not essential role in the generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of any desired specificity in vivo. The same goal can be achieved in vitro by expanding antigen-specific CD4+ T cells and retrovirally transducing them. In contrast, in vitro expansion of Tregs is Limited to antigens that have resulted in Treg generation in vivo. Antigen-specific Tregs can be used in cellular therapy with the goal to prevent autoimmune disease or even to interfere with established autoimmunity. The latter requires that the Tregs can suppress effector cells that have already caused harm, which is possible because of the antigen-dependent homing properties of Tregs, i.e. these cells can accumulate in antigen-draining lymph nodes and exit into inflamed tissue. Generally, the in vivo interference is dependent on cytokines such as transforming growth factor-β and interleukin-10 that were dispensable in in vivo analysis of immunosuppression. The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non-suppressed T cells.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalImmunological Reviews
Volume212
DOIs
StatePublished - Aug 1 2006

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Keywords

  • Autoimmune suppression
  • Foxp3
  • Regulatory T cells
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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