Homeostasis limits the development of mature CD8+ but not CD4+ thymocytes.

Details

Serval ID
serval:BIB_6573
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Homeostasis limits the development of mature CD8+ but not CD4+ thymocytes.
Journal
Journal of Immunology
Author(s)
van Meerwijk J.P., Marguerat S., MacDonald H.R.
ISSN
0022-1767
Publication state
Published
Issued date
1998
Peer-reviewed
Oui
Volume
160
Number
6
Pages
2730-2734
Language
english
Abstract
The involvement of a variety of clonal selection processes during the development of T lymphocytes in the thymus has been well established. Less information, however, is available on how homeostatic mechanisms may regulate the generation and maturation of thymocytes. To investigate this question, mixed radiation bone marrow chimeras were established in which wild-type T cell precursors capable of full maturation were diluted with precursors deficient in maturation potential because of targeted mutations of the RAG1 or TCR-alpha genes. In chimeras in which the majority of thymocytes are blocked at the CD4- CD8- CD25+ stage (RAG1 deficient), and only a small proportion of T cell precursors are of wild-type origin, we observed no difference in the maturation of wild-type CD4- CD8- CD25+ cells to the CD4+ CD8+ stage as compared with control chimeras. Therefore, the number of cell divisions occurring during this transition is fixed and not subject to homeostatic regulation. In contrast, in mixed chimeras in which the majority of thymocytes are blocked at the CD4+ CD8+ stage (TCR-alpha deficient), an increased efficiency of development of wild-type mature CD8+ cells was observed. Surprisingly, the rate of generation of mature CD4+ thymocytes was not affected in these chimeras. Thus, the number of selectable CD8 lineage thymocytes apparently saturates the selection mechanism in normal mice while the development of CD4 lineage cells seems to be limited only by the expression of a suitable TCR. These data may open the way to the identification of homeostatic mechanisms regulating thymic output and CD4/CD8 lineage commitment, and the development of means to modulate it.
Keywords
Animals, CD4-Positive T-Lymphocytes/physiology, CD8-Positive T-Lymphocytes/physiology, Hematopoietic Stem Cells/physiology, Homeostasis, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell/physiology, Receptors, Interleukin-2/analysis
Pubmed
Web of science
Create date
19/11/2007 12:43
Last modification date
20/08/2019 14:21
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