Autoreactive T Cells in Healthy Individuals

• Published in: The Journal of immunology (1950) Vol. 172; no. 10; pp. 5967 - 5972
• Main Authors: Danke, Nancy A, Koelle, David M, Yee, Cassian, Beheray, Sucheta, Kwok, William W
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.2004
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.10.5967

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.