Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4(+) T lymphocytes via an interleukin-2-dependent mechanism
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
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
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.
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Citation: Cell Immunol. 2009;256(1-2):86-91. Epub 2009 Feb 23. Link to article on publisher's site
Bishop KD, Harris JE, Mordes JP, Greiner DL, Rossini AA, Czech MP, Phillips NE. (2009). Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4(+) T lymphocytes via an interleukin-2-dependent mechanism. MD/PhD Program. Retrieved from https://escholarship.umassmed.edu/gsbs_mdphd/11