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PMID: 9565635 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A role for Fas in negative selection of thymocytes in vivo.

The Journal of experimental medicine ·Vol. 187 ·No. 9 ·1998-05-04 ·Pages 1427-38

Kishimoto H, Surh CD, Sprent J

Abstract

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1-100 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (</=1 microg) but not by high doses (100 microg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/immunology,metabolism CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Clone Cells/immunology Enterotoxins/immunology Flow Cytometry Immune Tolerance/immunology Mice Mice, Inbred Strains Mice, Transgenic Molecular Sequence Data Ovalbumin/immunology Peptide Fragments/immunology Receptors, Antigen, T-Cell/genetics Thymus Gland/physiology fas Receptor/physiology
Chemicals
Antibodies, Monoclonal Enterotoxins Peptide Fragments Receptors, Antigen, T-Cell fas Receptor enterotoxin B, staphylococcal Ovalbumin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kishimoto H
Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Surh C D
Sprent J
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44 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.187.9.1427
Published
1998-05-04
Pages
1427-38
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212270
Subset
IM
Grants
NCI NIH HHS · CA38355 · United States
NIAID NIH HHS · AI21487 · United States
NCI NIH HHS · CA25803 · United States
External Links
PubMed source DOI: 10.1084/jem.187.9.1427 PMC Full Text View journal details
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