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Thymic epithelial cell lines that mediate positive selection can also induce thymocyte clonal deletion
P Hugo1, J W Kappler, D I Godfrey
1Howard Hughes Medical Institute, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Journal of Immunology (Baltimore, Md. : 1950)
|February 1, 1994
Summary
Thymic epithelial cells can eliminate self-reactive T cells, a process called negative selection. These cells may also play a role in positive selection, indicating stromal cells orchestrate T-cell development.
Area of Science:
- Immunology
- Cell Biology
Background:
- Negative selection of autoreactive thymocytes primarily occurs in the thymus, mediated by bone marrow-derived cells.
- Thymic epithelial cells, a radioresistant population, have also been implicated in thymocyte deletion, particularly in response to endogenous superantigens.
Purpose of the Study:
- To investigate the capacity of thymic epithelial cell lines to induce negative selection of thymocytes reacting to staphylococcal enterotoxin A or B.
- To compare the efficiency of thymic epithelial cells in negative selection with that of thymic macrophages.
Main Methods:
- In vitro assessment of thymic epithelial cell lines' ability to activate T cell hybrids or delete CD4+CD8+ thymocytes in the presence of staphylococcal enterotoxin A or B.
- Phenotypic characterization of three distinct thymic cell lines.
Main Results:
- All tested thymic epithelial cell lines demonstrated the ability to activate T cell hybrids or delete specific thymocytes when exposed to staphylococcal enterotoxin A or B.
- The deletion efficiency mediated by thymic epithelial cells was comparable to that of thymic macrophages.
- These findings suggest that thymic epithelial cells, across various subsets, possess a general capacity for inducing thymocyte deletion.
Conclusions:
- Thymic epithelial cells are capable of mediating negative selection of thymocytes reacting to superantigens.
- Combined with previous findings on positive selection, this suggests a dual role for thymic stromal cells in orchestrating both positive and negative selection processes during T-cell development.