{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gupta S"],"funding":["NIAID NIH HHS","Medical Research Council","NINDS NIH HHS","PHS HHS"],"pagination":["2395-404"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3386804"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(7)"],"pubmed_abstract":["Tregs play a pivotal role in inducing and maintaining donor-specific transplant tolerance. The T cell immunoglobulin and mucin domain-3 protein (TIM-3) is expressed on many fully activated effector T cells. Along with program death 1 (PD-1), TIM-3 is used as a marker for exhausted effector T cells, and interaction with its ligand, galectin-9, leads to selective death of TIM-3+ cells. We report herein the presence of a galectin-9-sensitive CD4+FoxP3+TIM-3+ population of T cells, which arose from CD4+FoxP3+TIM-3- proliferating T cells in vitro and in vivo and were often PD-1+. These cells became very prominent among graft-infiltrating Tregs during allograft response. The frequency and number of TIM-3+ Tregs peaked at the time of graft rejection and declined thereafter. Moreover, these cells also arise in a tolerance-promoting donor-specific transfusion model, representing a pool of proliferating, donor-specific Tregs. Compared with TIM-3- Tregs, TIM-3+ Tregs, which are often PD-1+ as well, exhibited higher in vitro effector function and more robust expression of CD25, CD39, CD73, CTLA-4, IL-10, and TGF-β but not galectin-9. However, these TIM-3+ Tregs did not flourish when passively transferred to newly transplanted hosts. These data suggest that a heretofore unrecognized graft-infiltrating, short-lived subset of Tregs can restrain rejection."],"journal":["The Journal of clinical investigation"],"pubmed_title":["Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs."],"pmcid":["PMC3386804"],"funding_grant_id":["P01 AI041521-12S1","P0AIGF41521","AI41521","R01 AI037691","P01 NS038037","P01 AI073748","R01 NS045937","AI37691","MR/J006742/1","P01 AI073748-02","P01 AI041521"],"pubmed_authors":["Gupta S","Strom TB","Larocca R","Thornley TB","Gao W","Turka LA","Kuchroo VK"],"additional_accession":[]},"is_claimable":false,"name":"Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs.","description":"Tregs play a pivotal role in inducing and maintaining donor-specific transplant tolerance. The T cell immunoglobulin and mucin domain-3 protein (TIM-3) is expressed on many fully activated effector T cells. Along with program death 1 (PD-1), TIM-3 is used as a marker for exhausted effector T cells, and interaction with its ligand, galectin-9, leads to selective death of TIM-3+ cells. We report herein the presence of a galectin-9-sensitive CD4+FoxP3+TIM-3+ population of T cells, which arose from CD4+FoxP3+TIM-3- proliferating T cells in vitro and in vivo and were often PD-1+. These cells became very prominent among graft-infiltrating Tregs during allograft response. The frequency and number of TIM-3+ Tregs peaked at the time of graft rejection and declined thereafter. Moreover, these cells also arise in a tolerance-promoting donor-specific transfusion model, representing a pool of proliferating, donor-specific Tregs. Compared with TIM-3- Tregs, TIM-3+ Tregs, which are often PD-1+ as well, exhibited higher in vitro effector function and more robust expression of CD25, CD39, CD73, CTLA-4, IL-10, and TGF-β but not galectin-9. However, these TIM-3+ Tregs did not flourish when passively transferred to newly transplanted hosts. These data suggest that a heretofore unrecognized graft-infiltrating, short-lived subset of Tregs can restrain rejection.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jul","modification":"2025-04-05T13:20:16.399Z","creation":"2019-03-27T00:55:05Z"},"accession":"S-EPMC3386804","cross_references":{"pubmed":["22684103"],"doi":["10.1172/JCI45138","10.1172/jci45138"]}}