Document Detail


Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells.
MedLine Citation:
PMID:  16493037     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
More effective discrimination between CD4+CD25+ regulatory T cells (Treg) and activated T cells would significantly improve the current level of purification of Treg and their therapeutic application. We observed that approximately 90% of Treg (positive for the nuclear transcription factor Forkhead winged helix protein-3 and able to inhibit naive T cell proliferation) isolated from the spleens or lymph nodes of normal mice did not express significant levels of the inhibitory receptor programmed cell death-1 (PD-1) on their surface, but retained PD-1 intracellularly. An identical phenotype was also identified for human CD4+CD25(high) T cells isolated from peripheral blood of healthy volunteers. By contrast, activated T cells expressed high levels of surface PD-1 that paralleled up-regulation of CD25 during effector cell expansion. This distinction allowed us to isolate CD4+CD25+PD-1(-) T cells with suppressive activity from mice immunized with mature allogeneic dendritic cells. Although purification was limited to resting Treg because TCR ligation induced up-regulation of surface PD-1, this strategy nevertheless represents a valuable step toward more definitive characterization of Treg and their improved purification for therapeutic assessment.
Authors:
Giorgio Raimondi; William J Shufesky; Daisuke Tokita; Adrian E Morelli; Angus W Thomson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  176     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-22     Completed Date:  2006-04-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2808-16     Citation Subset:  AIM; IM    
Affiliation:
Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, PA 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antigens, Surface / biosynthesis,  genetics,  metabolism*
Apoptosis Regulatory Proteins / biosynthesis,  genetics,  metabolism*
Cell Compartmentation / immunology*
Cells, Cultured
Forkhead Transcription Factors / biosynthesis,  metabolism
G0 Phase / immunology*
Gene Expression Profiling
Humans
Intracellular Fluid / immunology,  metabolism
Lymphocyte Activation / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Molecular Sequence Data
Protein Transport / physiology
Receptors, Antigen, T-Cell / physiology
Receptors, Interleukin-2 / biosynthesis,  genetics
T-Lymphocytes, Regulatory / cytology,  immunology*,  metabolism*
Grant Support
ID/Acronym/Agency:
R01AI41011/AI/NIAID NIH HHS; R01AI60994/AI/NIAID NIH HHS; R01DK49745/DK/NIDDK NIH HHS; R01HL075512/HL/NHLBI NIH HHS; R01HL077545/HL/NHLBI NIH HHS; R21AI55027/AI/NIAID NIH HHS; R21HL69725/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Apoptosis Regulatory Proteins; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Pdcd1 protein, mouse; 0/Receptors, Antigen, T-Cell; 0/Receptors, Interleukin-2

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