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Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis
- Source :
- Gastroenterology; November 2003, Vol. 125 Issue: 5 p1379-1387, 9p
- Publication Year :
- 2003
-
Abstract
- Background & Aims:: Previous work has suggested that CD4^+ CD28^- or costimulation-independent T cells are increased in autoimmune diseases. In this study, we compared frequency and qualitative characteristics of autoreactive costimulation-independent or CD4^+ CD28^- T cells in primary biliary cirrhosis (PBC) by taking advantage of the well-defined immunodominant autoepitope of the E2 component of pyruvate dehydrogenase (PDC-E2). Methods:: We determined the frequency of costimulation-independent autoreactive T cells that respond to PDC-E2 163-176 and the frequency of CD4^+ CD28^- T cells. Finally, we determined the role of biliary epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a target cell for T-cell-mediated cytotoxicity. Results:: The precursor frequency of costimulation-independent CD4^+ T cells that respond to PDC-E2 163-176 and the frequency of CD4^+ CD28^- T cells were dramatically elevated in PBC. Furthermore, 2 types of T-cell clones that respond to PDC-E2 163-176 emerged from this study. One type was costimulation dependent and the other costimulation independent. Both types of clones lyse BEC in a similar effector target (E/T) ratio distribution. However, BEC did not help the proliferation of any T-cell clones. Furthermore, costimulation-independent T-cell clones do not become anergic by BEC. Conclusions:: In PBC, costimulation-independent autoreactive T cells, which do not become anergic, increase and maintain the autoimmune response. In controls, although autoantigens are expressed on BEC and autoantigen-reactive T cells exist around BEC, autoantigen-reactive T cells are costimulation dependent and will become anergic and maintain peripheral tolerance.
Details
- Language :
- English
- ISSN :
- 00165085 and 15280012
- Volume :
- 125
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Gastroenterology
- Publication Type :
- Periodical
- Accession number :
- ejs9906025
- Full Text :
- https://doi.org/10.1016/j.gastro.2003.07.013