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GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2002 Apr; Vol. 109 (7), pp. 895-903. - Publication Year :
- 2002
-
Abstract
- Insulin-dependent type 1 diabetes is an autoimmune disease mediated by T lymphocytes recognizing pancreatic islet cell antigens. Glutamic acid decarboxylase 65 (GAD65) appears to be an important autoantigen in the disease. However, T cells from both patients with type 1 diabetes and healthy subjects vigorously proliferate in response to GAD65 stimulation ex vivo, leading us to postulate that the critical event in the onset of human diabetes is the activation of autoreactive T cells. Thus, we investigated whether GAD65-reactive T cells in patients with diabetes functioned as previously activated memory T cells, no longer requiring a second, costimulatory signal for clonal expansion. We found that in patients with new-onset type 1 diabetes, GAD65-reactive T cells were strikingly less dependent on CD28 and B7-1 costimulation to enter into cell cycle and proliferate than were equivalent cells derived from healthy controls. We hypothesize that these autoreactive T cells have been activated in vivo and have differentiated into memory cells, suggesting a pathogenic role in type 1 diabetes. In addition, we observed different effects with selective blockade of either B7-1 or B7-2 molecules; B7-1 appears to deliver a negative signal by engaging CTLA-4, while B7-2 engagement of CD28 upregulates T cell proliferation and cytokine secretion.
- Subjects :
- Abatacept
Adult
Antigens, CD immunology
Antigens, Differentiation immunology
Autoimmunity
B7-1 Antigen immunology
B7-2 Antigen
CD28 Antigens immunology
CTLA-4 Antigen
Cell Division
Diabetes Mellitus, Type 1 blood
Female
Glutamate Decarboxylase pharmacology
Humans
Interferon-gamma biosynthesis
Interleukin-13 biosynthesis
Isoenzymes pharmacology
Male
Membrane Glycoproteins immunology
T-Lymphocytes cytology
T-Lymphocytes drug effects
Diabetes Mellitus, Type 1 immunology
Glutamate Decarboxylase immunology
Immunoconjugates
Isoenzymes immunology
Signal Transduction immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 109
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 11927616
- Full Text :
- https://doi.org/10.1172/JCI14114