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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 11 Jun 2010

Li XL, Ménoret S, Bezie S, Caron L, Chabannes D, Hill M, Halary F, Angin M, Heslan M, Usal C, Liang L, Guillonneau C, Le Mauff B, Cuturi MC, Josien R, Anegon I

Link to Pubmed [PMID] – 20543104

J. Immunol. 2010 Jul;185(2):823-33

Despite accumulating evidence for the importance of allospecific CD8(+) regulatory T cells (Tregs) in tolerant rodents and free immunosuppression transplant recipients, mechanisms underlying CD8(+) Treg-mediated tolerance remain unclear. By using a model of transplantation tolerance mediated by CD8(+) Tregs following CD40Ig treatment in rats, in this study, we show that the accumulation of tolerogenic CD8(+) Tregs and plasmacytoid dendritic cells (pDCs) in allograft and spleen but not lymph nodes was associated with tolerance induction in vascularized allograft recipients. pDCs preferentially induced tolerogenic CD8(+) Tregs to suppress CD4(+) effector cells responses to first-donor Ags in vitro. When tolerogenic CD8(+) Tregs were not in contact with CD4(+) effector cells, suppression was mediated by IDO. Contact with CD4(+) effector cells resulted in alternative suppressive mechanisms implicating IFN-gamma and fibroleukin-2. In vivo, both IDO and IFN-gamma were involved in tolerance induction, suggesting that contact with CD4(+) effector cells is crucial to modulate CD8(+) Tregs function in vivo. In conclusion, CD8(+) Tregs and pDCs interactions were necessary for suppression of CD4(+) T cells and involved different mechanisms modulated by the presence of cell contact between CD8(+) Tregs, pDCs, and CD4(+) effector cells.

http://www.ncbi.nlm.nih.gov/pubmed/20543104