Role of the naive and memory CD4+T-cell repertoire in transplantation

Details

Serval ID
serval:BIB_D456292A9E86
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Role of the naive and memory CD4+T-cell repertoire in transplantation
Title of the conference
Annual meeting of the Swiss Society of Nephrology
Author(s)
Golshayan D., Wyss J.C., Hernandez-Fuentes M., Pascual M., Lechler R.
Address
Interlaken, Switzerland, December 2-4, 2009
ISBN
1424-7860
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
139
Series
Swiss Medical Weekly
Pages
3S
Language
english
Notes
Publication type : Meeting Abstract
Abstract
Purpose: The exact role of individual T cell-subsets in the
development of rejection is not clearly defined. Given their distinct
phenotypes, effector functions and trafficking patterns, naïve
(CD45RBhiCD44lo) and memory (CD45RBloCD44hi) T cells may play
distinct roles in anti-donor immunity after transplantation. Furthermore,
only the CD4+CD45RBlo population contains CD4+CD25+ T cells,
a subset with suppressive functions playing a major role in the
maintenance of peripheral tolerance. The aim of this work was to study
the contribution of these individual subsets in alloresponses via the
direct and indirect pathways using a murine experimental model.
Methods and materials: Purified naïve or memory CD4+ T cells
were adoptively transferred into lymphopenic mice undergoing a skin
allograft. Donor to recipient MHC combinations were chosen in order
to study the direct and the indirect pathways of allorecognition
separately. Graft survival and in vivo expansion, effector function and
trafficking of the transferred T cells was assessed at different time
points after transplantation.
Results: We found that the cross-reactive CD4+CD45RBlo memory
T-cell pool was heterogeneous and contained cells with regulatory
potentials, both in the CD4+CD25+ and CD4+CD25-populations.
CD4+ T cells capable of inducing strong primary alloreactive
responses in vitro and rejection of a first allograft in vivo were mainly
contained within the CD45RBhi naïve CD4+ T-cell compartment.
CD4+CD45RBlo T cells proliferated less abundantly to allogeneic
stimulation than their naïve counterparts both in vitro and in vivo, and
allowed prolonged allograft survival even after the depletion of the
CD4+CD25+ subset. Interestingly, CD4+CD25-CD45RBlo T cells
were capable of prolonging allograft survival, mainly when the indirect
pathway was the only mechanism of allorecognition. The indirect
pathway response, which was shown to drive true chronic rejection
and contribute to chronic allograft dysfunction, was predominantly
mediated by naïve CD4+ T cells.
Conclusion: This work provides new insights into the mechanisms
that drive allograft rejection and should help develop new clinical
immunosuppressive protocols. In particular, our results highlight the
importance of selectively targeting individual T-cell subsets to prevent
graft rejection but at the same time maintain immune protective
responses to common pathogens.
Keywords
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Web of science
Create date
27/07/2010 11:52
Last modification date
20/08/2019 15:54
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