Impaired negative selection of T cells in Hodgkin's disease antigen CD30-deficient mice.
CD30 is found on Reed-Sternberg cells of Hodgkin's disease and on a variety of non-Hodgkin's lymphoma cells and is up-regulated on cells after Epstein-Barr virus, human T cell leukemia virus, and HIV infections. We report here that the thymus in CD30-deficient mice contains elevated numbers of thymocytes. Activation-induced death of thymocytes after CD3 cross-linking is impaired both in vitro and in vivo. Breeding the CD30 mutation separately into alpha beta TCR-or gamma delta TCR-transgenic mice revealed a gross defect in negative but not positive selection. Thus, like TNF-receptors and Fas/Apo-1, the CD30 receptor is involved in cell death signaling. It is also an important coreceptor that participates in thymic deletion.
Amakawa
R
R
Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Hakem
A
A
Kundig
T M
TM
Matsuyama
T
T
Simard
J J
JJ
Timms
E
E
Wakeham
A
A
Mittruecker
H W
HW
Griesser
H
H
Takimoto
H
H
Schmits
R
R
Shahinian
A
A
Ohashi
P
P
Penninger
J M
JM
Mak
T W
TW
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D017353:Gene Deletion; D015870:Gene Expression / Q000276:immunology; D006689:Hodgkin Disease / Q000276:immunology; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D013950:Thymus Gland / Q000166:cytology / Q000473:pathology
D017730:Ki-1 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018089:Superantigens