Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells?
CD28 and CTLA-4 are prototypal co-stimulatory and co-inhibitory cell surface signaling molecules interacting with CD80/86, known to be critical for immune response initiation and regulation, respectively. Initial bench-to-beside translation, two decades ago, resulted in the development of CTLA4-Ig,...
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doaj-6e51015dad0e4931a54733eb9e953b152020-11-24T22:50:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-08-01610.3389/fimmu.2015.00411153996Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells?Simon eVille0Simon eVille1Nicolas ePoirier2Nicolas ePoirier3Nicolas ePoirier4Gilles eBlancho5Gilles eBlancho6Bernard eVanhove7Bernard eVanhove8Bernard eVanhove9Institut de Transplantation Urologie Néphrologie (ITUN), Université de NantesINSERM UMR1064Institut de Transplantation Urologie Néphrologie (ITUN), Université de NantesINSERM UMR1064Effimune SASInstitut de Transplantation Urologie Néphrologie (ITUN), Université de NantesINSERM UMR1064Institut de Transplantation Urologie Néphrologie (ITUN), Université de NantesINSERM UMR1064Effimune SASCD28 and CTLA-4 are prototypal co-stimulatory and co-inhibitory cell surface signaling molecules interacting with CD80/86, known to be critical for immune response initiation and regulation, respectively. Initial bench-to-beside translation, two decades ago, resulted in the development of CTLA4-Ig, a biologic which targets CD80/86 and prevents T-cell costimulation. In spite of its proven effectiveness in inhibiting allo-immune responses, particularly in murine models, clinical experience in kidney transplantation with belatacept (high affinity CTLA4-Ig molecule) reveals a high incidence of acute, cell-mediated rejection. Originally, the etiology of belatacept-resistant graft rejection was thought to be heterologous immunity, i.e. the cross-reactivity of the pool of memory T cells from pathogen specific immune responses with alloantigens. Recently, the standard view that memory T cells arise from effector cells after clonal contraction has been challenged by a developmental model, in which less differentiated memory T cells generate effector cells. This review delineates how this shift in paradigm, given the differences in co-stimulatory and co-inhibitory signal depending on the maturation stage, could profoundly affect our understanding of the CD28 / CTLA-4 / CD80/86 blockade and highlights the potential advantages of selectively targeting CD28, instead of CD80/86, to control post-transplant immune responses.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00411/fullTransplantation ImmunologyCTLA-4CD28costimulation blockadeeffector T cellsmemory T cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simon eVille Simon eVille Nicolas ePoirier Nicolas ePoirier Nicolas ePoirier Gilles eBlancho Gilles eBlancho Bernard eVanhove Bernard eVanhove Bernard eVanhove |
spellingShingle |
Simon eVille Simon eVille Nicolas ePoirier Nicolas ePoirier Nicolas ePoirier Gilles eBlancho Gilles eBlancho Bernard eVanhove Bernard eVanhove Bernard eVanhove Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? Frontiers in Immunology Transplantation Immunology CTLA-4 CD28 costimulation blockade effector T cells memory T cells |
author_facet |
Simon eVille Simon eVille Nicolas ePoirier Nicolas ePoirier Nicolas ePoirier Gilles eBlancho Gilles eBlancho Bernard eVanhove Bernard eVanhove Bernard eVanhove |
author_sort |
Simon eVille |
title |
Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? |
title_short |
Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? |
title_full |
Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? |
title_fullStr |
Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? |
title_full_unstemmed |
Costimulatory blockade of the CD28 / CD80-86 / CTLA-4 balance in transplantation: impact on memory T cells? |
title_sort |
costimulatory blockade of the cd28 / cd80-86 / ctla-4 balance in transplantation: impact on memory t cells? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2015-08-01 |
description |
CD28 and CTLA-4 are prototypal co-stimulatory and co-inhibitory cell surface signaling molecules interacting with CD80/86, known to be critical for immune response initiation and regulation, respectively. Initial bench-to-beside translation, two decades ago, resulted in the development of CTLA4-Ig, a biologic which targets CD80/86 and prevents T-cell costimulation. In spite of its proven effectiveness in inhibiting allo-immune responses, particularly in murine models, clinical experience in kidney transplantation with belatacept (high affinity CTLA4-Ig molecule) reveals a high incidence of acute, cell-mediated rejection. Originally, the etiology of belatacept-resistant graft rejection was thought to be heterologous immunity, i.e. the cross-reactivity of the pool of memory T cells from pathogen specific immune responses with alloantigens. Recently, the standard view that memory T cells arise from effector cells after clonal contraction has been challenged by a developmental model, in which less differentiated memory T cells generate effector cells. This review delineates how this shift in paradigm, given the differences in co-stimulatory and co-inhibitory signal depending on the maturation stage, could profoundly affect our understanding of the CD28 / CTLA-4 / CD80/86 blockade and highlights the potential advantages of selectively targeting CD28, instead of CD80/86, to control post-transplant immune responses. |
topic |
Transplantation Immunology CTLA-4 CD28 costimulation blockade effector T cells memory T cells |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00411/full |
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