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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Iwabuchi, K. Nakayama, K. Murphy, K. M. Loh, D. Y. Nishimura, T. Wang, F. Habu, S. Mccoy, R. L. |
| Description | Author Affiliation: Iwabuchi K ( Department of Medicine, Genetics, and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.); |
| Abstract | Thymocytes from DO10 T-cell-receptor transgenic mice undergo apoptosis, or programmed cell death, when chicken ovalbumin-(323-339) peptide is administered in vivo. Using DO10 mice thymocytes, we have now developed a simple in vitro model system that recapitulates the in vivo clonal-deletion process. When transgenic thymocytes were cocultured with fibroblasts, B cells, or thymic nurse cell lines (all bearing I-Ad) in the presence of chicken ovalbumin-(323-339), deletion of the transgenic TCR+CD4+CD8+ thymocytes was seen within 8-20 hr. Thymocytes designed to bear I-Ad on their surface could mediate the deletion themselves. Thus, thymocyte clonal deletion entirely depends on the stage at which the thymocytes are vulnerable to the onset of apoptosis, rather than on the nature of the peptide antigen-presenting cells. Furthermore, thymic nurse cell line TNC-R3.1 could cause deletion, strongly suggesting that some thymic epithelial/stromal components are potentially capable of participating in negative selection. In all cases examined, little deletion could be induced at a peptide concentration less than 10 nM, thus defining the minimum amount of peptide antigen required for negative selection. The peptide-dependent in vitro negative-selection system will allow further dissection of the molecular and cellular processes involved in clonal deletion due to apoptosis in the thymus. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 89 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1992-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Lymphocyte Depletion Receptors, Antigen, T-Cell Immunology T-Lymphocytes Amino Acid Sequence Animals Antigen-Presenting Cells Antigens, CD4 Antigens, CD8 Apoptosis B-Lymphocytes Cell Line Cells, Cultured Crosses, Genetic DNA Genetics Isolation & Purification Flow Cytometry Genes, MHC Class II Mice Mice, Inbred BALB C Mice, Transgenic Molecular Sequence Data Ovalbumin Peptides Chemical Synthesis Pharmacology Cytology Drug Effects Thymus Gland Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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