Title

Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4(+) T lymphocytes via an interleukin-2-dependent mechanism

UMMS Affiliation

Graduate School of Biomedical Sciences, MD/PhD Program; Program in Molecular Medicine; Department of Medicine, Diabetes Division; Department of Medicine, Division of Endocrinology and Metabolism

Date

2-24-2009

Document Type

Article

Medical Subject Headings

Animals; Antigens; Antigens, Surface; Apoptosis Regulatory Proteins; inhibitors; Base Sequence; CD4-Positive T-Lymphocytes; Cell Line; Cell Proliferation; Clonal Anergy; Columbidae; Cytochromes c; DNA Primers; Interleukin-2; Mice; Mice, Inbred BALB C; Phenotype; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Transfection; Transplantation Tolerance

Abstract

Recent studies have implicated the cell surface receptor Programmed Death-1 (PD-1) in numerous models of T cell anergy, though the specific mechanisms by which the PD-1 signal maintains tolerance is not clear. We demonstrate that the depletion of PD-1 with siRNA results in a complete reversal of clonal anergy in the A.E7 T cell model, suggesting that the mechanism by which PD-1 maintains the anergic phenotype is a T-cell-intrinsic phenomenon, and not one dependent on other cell populations in vivo. We have also shown that the neutralization of IL-2 during restimulation abrogates the effect of PD-1 depletion, suggesting that tolerance mediated by PD-1 is wholly IL-2 dependent, and likewise intrinsic to the tolerized cells.

Rights and Permissions

Citation: Cell Immunol. 2009;256(1-2):86-91. Epub 2009 Feb 23. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

19230866