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| Content Provider | PubMed Central |
|---|---|
| Author | Stacy, Sue Williams, Earlanda L. Standifer, Nathan E. Pasquali, Amanda Krolick, Keith A. Infante, Anthony J. Kraig, Ellen |
| Abstract | Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, like myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor (AChR), the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica AChR (TAChR) α-chain as a neo-self antigen. T cells from young transgenic mice had been shown to be tolerant to p146-162, the TAChR α-chain peptide that dominated young nontransgenic T-cell responses in vitro. The immunodominance of p146-162 was not lost with age; fine specificity was preserved. Moreover, T-cell tolerance to p146-162, as well as to other epitopes of the TAChR α chain extracellular domain, was maintained in old transgenic mice. Even multiple TAChR immunizations coupled with the MG-enhancing cytokine, IL-12, did not break tolerance. Additionally, T cells exhibiting CD4 upregulation, an early activation marker, were reduced in frequency equivalently in old and young transgenic animals suggesting that immune regulation in this model was not impacted by aging. Moreover, B-cell tolerance was also maintained with age. The persistence of immune tolerance was accompanied by an increase in the proportion of Tregs; it is speculated that this may compensate for deficiencies in central tolerance that occur due to thymic involution. In summary, our study reveals, for the first time, that some immune tolerance mechanisms do survive aging; this suggests that certain late onset autoimmune disorders may be induced by a specific insult that disrupts immune homeostasis. |
| Related Links | http://dx.doi.org/10.4049/jimmunol.0901618 |
| Starting Page | 6067 |
| File Format | |
| ISSN | 15506606 |
| e-ISSN | 15506606 |
| Journal | Journal of immunology (Baltimore, Md. : 1950) |
| Issue Number | 11 |
| Volume Number | 184 |
| Language | English |
| Publisher Date | 2010-06-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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