B7 blockade prevents activation-induced cell death of thymocytes.
Although both B7 and its counter-receptor CD28 are expressed in the thymus, the role of B7 in thymic selection is not clear. We investigated the role of B7 in intrathymic deletion of antigen-specific T cells using a TCR transgenic model specific for antigen ovalbumin (OVA) and H-2Ad. Intraperitoneal injection of OVA induced apoptosis of thymocytes and drastic reduction of thymocyte numbers. This was significantly inhibited by co-injection of CTLA-4-Ig which blocks B7 co-stimulation. Deletion of T cells in the thymus following i.p. injection of OVA was associated with T cell pre-activation as demonstrated by T cell proliferation and cytokine production. Injection of CTLA-4-Ig blocked all these activation events and rescued thymocytes from activation-induced cell death. These results demonstrate that B7 is required for the activation-induced cell death of MHC class II-restricted thymocytes in vivo.
Samoilova
E B
EB
Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Horton
J L
JL
Bassiri
H
H
Zhang
H
H
Linsley
P S
PS
Carding
S R
SR
Chen
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018122:B7-1 Antigen; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin