Document Type : Original Article
Authors
- Fathollah Kalantar 1
- Mohammad Hossein Dabbaghmanesh 2
- Emanuela Martinuzzi 3
- Mohsen Moghadami 4
- Zahra Amirghofran 1, 5, 6
1 Department of Immunology
2 Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 Cochin Institute, Paris, France
4 HIV/AIDS Research Center
5 Autoimmune Disease Research Center
6 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction.
Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 + T-cells specific for this protein might be present in T2D patients.
Methods: Peripheral blood mononuclear cells (PBMC) were obtained from human leukocyte antigen (HLA)-A2 + T2D patients and non-diabetic healthy subjects. Cells were then screened for peptide recognition using ELISPOT assay for the presence of IFN-γ producing CD8 + T-cells against two HLA Class I-restricted epitopes derived from IAPP (IAPP 5-13 and IAPP9-17) and common viral antigenic minimal epitopes Flu MP 58-66, CMV495–503, EBV280–288 and HIV77–85 as controls.
Results: A total of 36.4% of patients and 56.2% of healthy subjects showed a response against IAPP 5-13 peptide. No significant difference in response against this peptide was noted between the patients and the healthy donors. With respect to peptide IAPP 9-17, although healthy subjects showed a higher mean number of spot forming cells than the patients, the difference was not significant; 36.4% of patients and 37.5% of controls responded to this peptide. The response of healthy subjects to the common viral peptides was stronger than that of the patients, though the result was not significant.
Conclusions: It is unlikely that IAPP would be a target for CD8+ T-cells in diabetic patients; however, the trend observed toward a lower response of T2D patients against IAPP and common viral peptides may imply a decreased immune response in these patients.
Keywords
)