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| IMMUNIZATION WITH THE LARGER ISOFORM OF MOUSE GLUTAMIC-ACID DECARBOXYLASE (GAD(67)) PREVENTS AUTOIMMUNE DIABETES IN NOD MICE |
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| Author(s): ELLIOTT JF, QIN HY, BHATTI S, SMITH DK, SINGH RK, DILLON T, LAUZON J, SINGH B |
| Source: DIABETES Volume: 43 Issue: 12 Pages: 1494-1499 Published: DEC 1994 |
| Times Cited: 109 References: 30 |
| Abstract: The 65-kDa isoform of glutamic acid decarboxylase (GAD(65)) has been implicated in autoimmune diabetes in NOD mice, but the role of the 67-kDa GAD isoform (GAD(67)) is less clear. We found that immunization of 4-week-old NOD mice with purified recombinant mouse GAD(67) prevented or significantly delayed the onset of diabetes. To further explore this phenomenon, we characterized anti-GAD(67) immune responses in naive and GAD-immunized NOD mice. Anti-GAD(67) antibodies titers were relatively low in naive mice at all ages, but a single immunization with GAD(67) at 4 weeks induced high titers of anti-GAD antibodies by 6 weeks of age. in both 4-weekold and diabetic NOD mice, there were significant endogenous T-cell proliferative responses against purified recombinant mouse GAD(67). These T-cell proliferative responses were blocked by anti-I-A(NOD) and anti-CD4 antibodies. To characterize the anti-GAD T-cell responses in the NOD mice, we established T-cell Lines and T-cell clones which recognized GAD(65), and we used recombinant subfragments of GAD to localize the predominant T-cell epitopes in GAD(67). T-cells from naive NOD mice proliferated in response to all GAD subfragments, whereas T-cells horn diabetic mice responded primarily to the COOH-terminal 83 amino acids of GAD(67). These results suggest that GAD(67) is an autoantigen in IDDM and immunization of prediabetic NOD mice with GAD(67) can prevent the onset of diabetes. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WESTERN ONTARIO, DEPT MICROBIOL & IMMUNOL, LONDON N6A 5C1, ON CANADA
2. UNIV ALBERTA, DEPT IMMUNOL, EDMONTON, AB CANADA
3. UNIV ALBERTA, DEPT MED MICROBIOL & INFECT DIS, EDMONTON, AB CANADA
4. ROBARTS RES INST, LONDON, ENGLAND |
| Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314 |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: PV463 |
| ISSN: 0012-1797 |
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