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PMID: 10429671 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Several different cell surface molecules control negative selection of medullary thymocytes.

The Journal of experimental medicine ·Vol. 190 ·No. 1 ·1999-07-05 ·Pages 65-73

Kishimoto H, Sprent J

Abstract

Repeated attempts to show that costimulation for negative selection is controlled by a single cell surface molecule have been unsuccessful. Thus, negative selection may involve multiple cell surface molecules acting in consort. In support of this idea, we show here that at least three cell surface molecules, namely CD28, CD5, and CD43, contribute to Fas-independent negative selection of the tolerance-susceptible population of heat-stable antigen (HSA)hiCD4+8- cells found in the medulla. The costimulatory function of these three molecules can be blocked by certain cytokines, IL-4 and IL-7, and coinjecting these cytokines with antigen in vivo abolishes negative selection; Fas-dependent negative selection, however, is maintained. The results suggest that efficient negative selection requires the combined functions of at least four cell surface molecules: CD28, CD5, CD43, and Fas.

MeSH Terms
Animals Antigens, CD Apoptosis CD28 Antigens/immunology CD4 Antigens/immunology CD5 Antigens/immunology CD8 Antigens/immunology Interleukin-4/immunology Interleukin-7/immunology Leukosialin Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell/immunology Sialoglycoproteins/immunology Surface Properties Thymus Gland/cytology,immunology
Chemicals
Antigens, CD CD28 Antigens CD4 Antigens CD5 Antigens CD8 Antigens Interleukin-7 Leukosialin Receptors, Antigen, T-Cell Sialoglycoproteins Spn protein, mouse Interleukin-4
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kishimoto H
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Sprent J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.190.1.65
Published
1999-07-05
Pages
65-73
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195556
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.190.1.65 PMC Full Text View journal details
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