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Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic murine T cells activated by specific peptide.

X Z Yu, L Zhu, J E Davis, J Y Tso, J A Hansen and C Anasetti
J Immunol October 15, 1996, 157 (8) 3420-3429;
X Z Yu
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L Zhu
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J E Davis
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J Y Tso
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J A Hansen
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C Anasetti
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Abstract

Peripheral T cell tolerance can be achieved through deletion of mature CD4+ cells activated by high dose Ag. We tested whether apoptosis of peripheral CD4+ cells could be induced by a stimulatory dose of Ag plus a soluble ligand to the nonpolymorphic epsilon-chain of the TCR-associated CD3 complex. CD4+ T cells from the DO10 mouse express a transgenic TCR-alphabeta specific for OVA peptide 323-339 presented by I-A(d). OVA alone induced clonal activation and expansion of peripheral CD4+/TCR transgene+ cells. Simultaneous exposure to specific Ag plus soluble anti-CD3 Fos, a nonmitogenic anti-CD3epsilon genetically engineered F(ab')2-like Ab, blocked expansion and induced death of CD4+/TCR transgene+ cells, but not CD4+/TCR transgene- T cells. In contrast, a mitogenic anti-CD3epsilon Ab induced polyclonal activation and nonselective T cell death. Sequential stimulation by Ag followed by anti-CD3 Fos also induced death of TCR transgene+ cells, whereas stimulation by anti-CD3 Fos followed by Ag did not affect cell viability or function. Anti-CD3 Fos-induced death was associated with DNA fragmentation characteristic of apoptosis, was facilitated by IL-2, and was initiated by stimulation during the S-G2 phases of the cell cycle. Anti-CD3 Fos could induce deletion of Ag-activated T cells by apoptosis in vivo. Thus, a soluble, non-Fc-binding anti-CD3 Ab can induce programmed cell death of Ag-activated peripheral CD4+ T cells by CD3epsilon cross-linking during S or G2. Peripheral T cell deletion by activation-driven apoptosis is under cell cycle control and can be exploited to achieve selective immunosuppression by nonmitogenic anti-CD3epsilon Abs.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 8
15 Oct 1996
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Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic murine T cells activated by specific peptide.
X Z Yu, L Zhu, J E Davis, J Y Tso, J A Hansen, C Anasetti
The Journal of Immunology October 15, 1996, 157 (8) 3420-3429;

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Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic murine T cells activated by specific peptide.
X Z Yu, L Zhu, J E Davis, J Y Tso, J A Hansen, C Anasetti
The Journal of Immunology October 15, 1996, 157 (8) 3420-3429;
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Print ISSN 0022-1767        Online ISSN 1550-6606