Autoreactive T cells in healthy individuals.
The presence of autoreactive CD4(+) T cells in the peripheral blood of healthy human subjects was investigated after removal of CD4(+)CD25(+) regulatory T cells (Treg). CD4(+) T cells that were directed against the type 1 diabetes-associated autoantigen glutamic acid decarboxylase 65, the melanocyte differentiation Ag tyrosinase, and the cancer/testis tumor Ag NY-ESO-1 were readily derived from PBMC of healthy individuals. These autoreactive T cells could be visualized, using Ag-specific class II tetramer reagents, in the peripheral blood of most individuals examined. Addition of CD4(+)CD25(+) Treg back to the CD4(+)CD25(-) population suppressed the expansion of the autoreactive T cells. Autoreactive T cells were cloned based on tetramer binding, and expressed characteristic activation markers upon self-Ag stimulation. These results show that autoreactive T cells are present in most healthy individuals and that Treg likely play an important role of keeping these autoreactive T cells in check.
Danke
Nancy A
NA
Benaroya Research Institute, Virginia Mason, Seattle, WA 98101, USA.
Koelle
David M
DM
Yee
Cassian
C
Beheray
Sucheta
S
Kwok
William W
WW
D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000097:blood; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology; D014442:Monophenol Monooxygenase / Q000097:blood / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D001324:Autoantigens; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D007527:Isoenzymes; D008565:Membrane Proteins; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D014442:Monophenol Monooxygenase; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2