Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4(+) T lymphocytes via an interleukin-2-dependent mechanism.
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.
Bishop
Kenneth D
KD
University of Massachusetts Medical School, Worcester, 01655, USA.
Harris
John E
JE
Mordes
John P
JP
Greiner
Dale L
DL
Rossini
Aldo A
AA
Czech
Michael P
MP
Phillips
Nancy E
NE
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D010856:Columbidae; D045304:Cytochromes c / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology
D000941:Antigens; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D007376:Interleukin-2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D045304:Cytochromes c