期刊
JOURNAL OF IMMUNOLOGY
卷 176, 期 5, 页码 2808-2816出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.176.5.2808
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资金
- NHLBI NIH HHS [R01HL075512, R21HL69725, R01HL077545] Funding Source: Medline
- NIAID NIH HHS [R01AI41011, R21AI55027, R01AI60994] Funding Source: Medline
- NIDDK NIH HHS [R01DK49745] Funding Source: Medline
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 similar to 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.
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