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- Title
GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes.
- Authors
Reijonen, Helena; Mallone, Roberto; Heninger, Anne-Kristin; Laughlin, Elsa M.; Kochik, Sharon A.; Falk, Ben; Kwok, William W.; Greenbaum, Carla; Nepom, Gerald T.
- Abstract
Negative selection of self-reactive T-cells during thymic development, along with activation-induced cell death in peripheral lymphocytes, is designed to limit the expansion and persistence of autoreactive T-cells. Autoreactive T-cells are nevertheless present, both in patients with type 1 diabetes and in at-risk subjects. By using MHC class II tetramers to probe the T-cell receptor (TcR) specificity and avidity of GAD65 reactive T-cell clones isolated from patients with type 1 diabetes, we identified high-avidity CD4+ T-cells in peripheral blood, coexisting with low-avidity cells directed to the same GAD65 epitope specificity. A variety of cytokine patterns was observed, even among T-cells with high MHC-peptide avidity, and the clones utilize a biased set of TcR genes that favor two combinations, Valpha12-beta5.1 and Valpha17-Vbeta4. Presence of these high-avidity TcRs indicates a failure to delete autoreactive T-cells that likely arise from oligoclonal expansion in response to autoantigen exposure during the progression of type 1 diabetes.
- Subjects
DIABETES; CARBOHYDRATE intolerance; GENES; HEREDITY; T cells; ANTIGENS; IMMUNITY; ANTIGEN-antibody reactions; AUTOANTIBODIES; BLOOD donors; CELL receptors; COMPARATIVE studies; ENZYMES; IMMUNOLOGY technique; TYPE 1 diabetes; ISOENZYMES; RESEARCH methodology; MEDICAL cooperation; REFERENCE values; RESEARCH; HLA-B27 antigen; EVALUATION research; BLOOD
- Publication
Diabetes, 2004, Vol 53, Issue 8, p1987
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.8.1987