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Proteome Analysis Reveals Caspase Activation in Hyporesponsive CD4 T Lymphocytes Induced in Vivo by the Oral Administration of Antigen.
- Source :
-
Journal of Biological Chemistry . 7/25/2003, Vol. 278 Issue 30, p27836. 8p. 2 Diagrams, 1 Chart, 8 Graphs. - Publication Year :
- 2003
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Abstract
- The oral administration of antigen can lead to systemic antigen-specific hyporesponsiveness, also known as oral tolerance. This phenomenon is a representative form of immune tolerance to exogenous antigen under physiological conditions. We have previously reported that long term feeding of dietary antigen to ovalbumin-specific T cell receptor (TCR) transgenic mice induced oral tolerance of peripheral T ceils with impairment in their TCR-induced calcium-signaling pathway. In this study, we utilized two-dimensional electrophoresis to compare intracellular protein expression patterns of orally tolerant and unsensitized CD4 T cells. We detected 26 increased and 16 decreased protein spots and identified 35 of these by mass spectrometry. The results indicated that the expression of caspases was up-regulated and that the protein levels of intact proteins susceptible to caspase cleavage, such as Grb2-related adaptor downstream of Shc (GADS), were decreased in orally tolerant CD4 T cells. Western blotting experiments confirmed that expression of the active form of caspase-3 and the antiapoptotic factor, X-linked inhibitor of apoptosis, were both up-regulated in orally tolerant CD4 T cells, which were found to be nonapoptotic. We further demonstrated that orally tolerant CD4 T cells could not form normal TCR signaling complexes associated with GADS and showed down-regulated phospholipase C-γ1 activation, which is likely to contribute to the impairment of TCR-induced calcium signaling. Our findings indicate that orally tolerant CD4 T cells up-regulate caspase activation and show decreased levels of caspase-targeted proteins, including TCR signaling-associated molecules, while up-regulating antiapoptotic factors, all of which appear to contribute to their unique tolerant characteristics. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LYMPHOCYTES
*ANTIGENS
*PROTEOMICS
*BIOCHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 278
- Issue :
- 30
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 10524969
- Full Text :
- https://doi.org/10.1074/jbc.M212820200