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Major histocompatibility complex class I restricted T-cell autoreactivity in human peripheral blood mononuclear cells.
- Source :
-
Cellular immunology [Cell Immunol] 2006 Mar; Vol. 240 (1), pp. 62-7. Date of Electronic Publication: 2006 Aug 01. - Publication Year :
- 2006
-
Abstract
- During selection in the thymus or any subsequent response, T-cells recognize peptides bound to major histocompatibility complex (MHC) molecules. Peptides produced by lysosomes or by proteasome/immunoproteasome stimulate CD4+ or CD8+ T-cell, respectively. Inflammation alters components of both antigen-processing pathways resulting in the production of different peptides. The role of such changes in self/non-self discrimination was examined in autologous mixed peripheral blood mononuclear cell cultures. Stimulator cells were incubated in the presence or absence of INF-gamma, with or without lysosome inhibitors (ammonium chloride/chloroquine), cathepsin inhibitor (E-64), or proteasome/immunoproteasome inhibitor (epoxomicin). Responder cells were added and zeta-chain phosphorylated forms were used as read out. INF-gamma did not affect zeta-chain phosphorylated forms, which means that the expected INF-gamma induced alterations in antigen processing machinery do not influence self/non-self discrimination. Surprisingly, the completely phosphorylated 23-kDa zeta-chain was always present except in the case of epoxomicin, indicating the presence of MHC class I restricted autoreactive CD8+ T-cells but not of MHC class II restricted autoreactive CD4+ T-cells, possibly due to more efficient negative selection in the thymus of the latter. Autoimmunity is prevented due to absence of help by CD4+ T-cells. This conclusion was confirmed by the lack of differences in IL-2 levels in cell culture supernatants, as well as, by the absence of differences in cell proliferation under the various conditions described above.
- Subjects :
- Cell Proliferation drug effects
Cell Separation
Cells, Cultured
Cysteine Endopeptidases metabolism
Humans
Interferon-gamma pharmacology
Interleukin-2 metabolism
Lysosomes drug effects
Phosphorylation drug effects
Proteasome Inhibitors
Subcellular Fractions
T-Lymphocytes cytology
Autoimmunity immunology
Histocompatibility Antigens Class I immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-8749
- Volume :
- 240
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16884707
- Full Text :
- https://doi.org/10.1016/j.cellimm.2006.06.006