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Hyporesponsiveness of CD4 T cells induced in oral tolerance is maintained by selective impairment in the TCR-induced calcium/NFAT signaling pathway resulting from caspase activation.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2004 Dec; Vol. 1029, pp. 344-5. - Publication Year :
- 2004
-
Abstract
- We examined intracellular signaling of hyporesponsive CD4 T cells induced by continuous feeding with high-dose antigen in a TCR transgenic mouse system. The results demonstrated a selective impairment in their TCR-induced calcium/NFAT-signaling pathway. Proteomic analysis revealed caspase activation in these cells, which resulted in cleavage of GADS. Further analysis of the TCR-signaling complex showed that GADS-LAT-SLP-76-associated PLC-gamma1 was decreased in both phosphorylation and association. Thus, as a consequence of caspase activation, orally tolerant CD4 T cells could not form normal TCR signaling complexes associated with GADS and showed downregulated PLC-gamma1 activation, which resulted in impairment of TCR-induced calcium signaling.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
Enzyme Activation
Lymphocyte Activation
Mice
Mice, Transgenic
NFATC Transcription Factors
Signal Transduction immunology
src Homology Domains
CD4-Positive T-Lymphocytes immunology
Calcium physiology
Caspases metabolism
DNA-Binding Proteins physiology
Immune Tolerance
Immunity, Mucosal
Nuclear Proteins physiology
Receptors, Antigen, T-Cell immunology
Signal Transduction physiology
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0077-8923
- Volume :
- 1029
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 15681776
- Full Text :
- https://doi.org/10.1196/annals.1309.016