Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus

Détails

ID Serval
serval:BIB_EC7C8559E073
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus
Périodique
Journal of Experimental Medicine
Auteur⸱e⸱s
Speiser  D. E., Chvatchko  Y., Zinkernagel  R. M., MacDonald  H. R.
ISSN
0022-1007 (Print)
Statut éditorial
Publié
Date de publication
11/1990
Volume
172
Numéro
5
Pages
1305-14
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 1
Résumé
Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self-tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a-specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a.
Mots-clé
Animals Bone Marrow/physiology/radiation effects *Bone Marrow Cells Bone Marrow Transplantation Cell Division/drug effects/physiology Clone Cells/*cytology Haplotypes Hematopoietic Stem Cells/cytology/immunology/physiology Heterozygote Homozygote Interleukin-2/pharmacology Lymphocyte Subsets Major Histocompatibility Complex/genetics Mice Mice, Inbred Strains/*genetics *Radiation Chimera T-Lymphocytes/*cytology/physiology/radiation effects Thymus Gland/cytology/physiology/radiation effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:33
Dernière modification de la notice
20/08/2019 16:14
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