Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, Neoplasm / blood
-
Antigens, Neoplasm / immunology
-
Autoantigens / blood
-
Autoantigens / immunology*
-
CD4-Positive T-Lymphocytes / enzymology
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / metabolism*
-
Cell Division / immunology
-
Cell Separation
-
Diabetes Mellitus, Type 1 / enzymology
-
Diabetes Mellitus, Type 1 / immunology
-
Epitopes, T-Lymphocyte / blood
-
Epitopes, T-Lymphocyte / immunology
-
Glutamate Decarboxylase / blood
-
Glutamate Decarboxylase / immunology
-
HLA-DR4 Antigen / blood
-
Humans
-
Isoenzymes / blood
-
Isoenzymes / immunology
-
Lymphocyte Activation / immunology*
-
Lymphocyte Count
-
Membrane Proteins / blood
-
Membrane Proteins / immunology
-
Monophenol Monooxygenase / blood
-
Monophenol Monooxygenase / immunology
-
Peptide Fragments / immunology
-
Receptors, Interleukin-2 / blood
-
Receptors, Interleukin-2 / immunology
-
T-Lymphocyte Subsets / enzymology
-
T-Lymphocyte Subsets / immunology*
-
T-Lymphocyte Subsets / metabolism*
-
T-Lymphocytes, Regulatory / immunology
-
T-Lymphocytes, Regulatory / metabolism
Substances
-
Antigens, Neoplasm
-
Autoantigens
-
CTAG1B protein, human
-
Epitopes, T-Lymphocyte
-
HLA-DR4 Antigen
-
Isoenzymes
-
Membrane Proteins
-
Peptide Fragments
-
Receptors, Interleukin-2
-
Monophenol Monooxygenase
-
Glutamate Decarboxylase
-
glutamate decarboxylase 2