Direct alloreactivity is more susceptible to regulation by natural regulatory T cells than indirect alloreactivity.

Grégory Noël; Meriam Belghith; Benoit Bélanger; Caroline Leduc; Claude Daniel

Direct alloreactivity is more susceptible to regulation by natural regulatory T cells than indirect alloreactivity.

Grégory Noël ¹ Meriam Belghith ¹ Benoit Bélanger ¹ Caroline Leduc ¹ Claude Daniel ^{1, *}

* Corresponding author

Abstract : The contribution of natural CD4(+)CD25(+) regulatory T cells (nTregs) in controlling graft rejection and the mechanism used remain controversial. Using the duality of the 2.102 TCR Ag recognition, we were able to study, for the first time to our knowledge, the involvement of nTregs in the two pathways of allorecognition in a murine adoptive transfer model in which TCR-transgenic nTregs were or were not depleted before transplantation. We show that nTregs used at a physiological ratio were able to delay graft rejection after direct alloreactivity by controlling proliferation and differentiation of alloreactive CD4(+) conventional T cells in draining lymph nodes. In contrast, similar results were found in the indirect alloreactivity pathway only when nTregs were used in high numbers. In the latter pathway, nTregs used at a physiological ratio failed to delay graft rejection and to control proliferation of conventional T cells. These results support recent therapeutic approaches aimed at producing and using in vitro Ag-specific Foxp3(+) nTregs to control graft rejection in transplantation. Finally, late inhibition of Th1 differentiation was shown in indirect alloreactivity, but this suppression could also be mediated by Foxp3(+)-induced Tregs.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Cellular Biology

Complete list of metadatas

Cited literature [35 references] Display Hide Download

https://hal-riip.archives-ouvertes.fr/pasteur-01132015
Contributor : Michel Courcelles <>
Submitted on : Monday, March 16, 2015 - 3:13:52 PM
Last modification on : Monday, October 8, 2018 - 5:44:05 PM
Long-term archiving on : Wednesday, June 17, 2015 - 1:05:15 PM

J Immunol-2013-Noël-3764-71....

Files produced by the author(s)

Direct alloreactivity is more susceptible to regulation by natural regulatory T cells than indirect alloreactivity.

File

Identifiers

Collections

Citation

Export

Metrics

82

170

Contact

Direct alloreactivity is more susceptible to regulation by natural regulatory T cells than indirect alloreactivity.

File

Identifiers

Collections

Citation

Export

Share

Metrics

82

170

Contact