Differential Effects of Peptide Diversity and Stromal Cell Type in Positive and Negative Selection in the Thymus

Thymocyte positive selection results in maturation to the single-positive stage, while negative selection results in death by apoptosis. Although kinetic analyses indicate only 3-5% of CD4+ 8+ cells reach the single-positive stage, the balance of positive and negative selection and the nature and qu...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 1998-12, Vol.161 (12), p.6599-6603
Main Authors: Anderson, Graham, Partington, Katharine M, Jenkinson, Eric J
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antigen Presentation
Apoptosis
CD4-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - cytology
Clonal Deletion - physiology
Dendritic Cells - physiology
Epithelial Cells - physiology
H-2 Antigens - immunology
Histocompatibility Antigens Class II - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Peptide Fragments - immunology
Stromal Cells - physiology
T-Lymphocyte Subsets - cytology
Thymus Gland - cytology
Thymus Gland - embryology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Thymocyte positive selection results in maturation to the single-positive stage, while negative selection results in death by apoptosis. Although kinetic analyses indicate only 3-5% of CD4+ 8+ cells reach the single-positive stage, the balance of positive and negative selection and the nature and quantity of cells mediating maximal negative selection are uncertain. Here, using a system where the number and type of stromal cells and thymocytes can be controlled, we investigated the maturation of CD4+ 8+ thymocytes in the presence or absence of thymic epithelium and dendritic cells (DC) from wild-type (wt) and H-2M(-/-) mice expressing different peptide arrays. We find that titration of wt DC into reaggregates of wt epithelium has a dramatic effect on the number of CD4+ cells generated, with 1% DC causing a maximal 80% reduction. Moreover, while addition of 1% wt DC into cultures of H-2M(-/-) epithelium causes a 90% reduction in CD4+ cells, no effect was observed when similar numbers of wt thymic epithelium were added. Collectively, these data provide the first accurate indication of the quantity and quality of stromal cells required for maximal negative selection in the thymus, demonstrate the importance of peptide diversity in T cell selection, and highlight a large degree of overlap between positive and negative selection events.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.161.12.6599