Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 1997 Dec 1;186(11):1911–1922. doi: 10.1084/jem.186.11.1911

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).

PMC Copyright notice

Only TCR-CD28–stimulated DP thymocytes die in response to TCR-CD28 coengagement. (a) TCR-CD28 stimulation will not kill bystander CD28 KO DP thymocytes. Individual populations of DP thymocytes from wild-type B6 mice and CD28 KO mice were cultured and stimulated independently with platebound antibodies. % Cell death of each population of DP thymocytes was quantitated and normalized as described in Materials and Methods. (b) Experimental design. DP thymocytes from wild-type mice (CD28⁺Ly5.2⁺) were mixed in a 1:1 ratio with DP thymocytes from CD28-deficient mice (CD28^−/−Ly 5.1⁺) and stimulated by platebound anti–TCR-β and anti-CD28. Thymocytes were harvested after overnight culture and percent cell death in each population was determined. CD28^+/+ and CD28^−/− DP thymocytes were distinguished by the presence or absence of Ly5.1 staining. (c) Bystander CD28 KO DP thymocytes are not killed by TCR-CD28 signals. DP thymocytes were isolated from wild-type and CD28-deficient (CD28 KO) mice which differed in Ly5 expression such that wild-type DP thymocytes were Ly5.2⁺ and CD28 KO thymocytes were Ly5.1⁺. Harvested cells were stained with both anti-Ly5.1 antibody and EtBr to determine cell death in each population of cocultured DP thymocytes. Percent cell death was quantitated and normalized as described in Materials and Methods. (d) Schematic of the mechanism by which TCR-CD28 coengagement kills DP thymocytes. This figure illustrates two possible CD28-dependent mechanisms of TCR-mediated apoptosis of DP thymocytes, both of which result in death exclusively of TCR-CD28–stimulated DP thymocytes. The upper figure (i) illustrates one scenario in which simultaneous coengagement of TCR and CD28 molecules directly and cell-autonomously induces an apoptotic program. The lower figure (ii) illustrates an alternative scenario in which simultaneous coengagement of TCR and CD28 induces expression of a death domain containing receptor (Y) that signals apoptosis upon interaction with its ligand (Y-L, Y ligand) that is also expressed on DP thymocytes. In this latter case, the ligand could conceivably engage the death receptor in either cis or trans.

Only TCR-CD28–stimulated DP thymocytes die in response to TCR-CD28 coengagement. (a) TCR-CD28 stimulation will not kill bystander CD28 KO DP thymocytes. Individual populations of DP thymocytes from wild-type B6 mice and CD28 KO mice were cultured and stimulated independently with platebound antibodies. % Cell death of each population of DP thymocytes was quantitated and normalized as described in Materials and Methods. (b) Experimental design. DP thymocytes from wild-type mice (CD28⁺Ly5.2⁺) were mixed in a 1:1 ratio with DP thymocytes from CD28-deficient mice (CD28^−/−Ly 5.1⁺) and stimulated by platebound anti–TCR-β and anti-CD28. Thymocytes were harvested after overnight culture and percent cell death in each population was determined. CD28^+/+ and CD28^−/− DP thymocytes were distinguished by the presence or absence of Ly5.1 staining. (c) Bystander CD28 KO DP thymocytes are not killed by TCR-CD28 signals. DP thymocytes were isolated from wild-type and CD28-deficient (CD28 KO) mice which differed in Ly5 expression such that wild-type DP thymocytes were Ly5.2⁺ and CD28 KO thymocytes were Ly5.1⁺. Harvested cells were stained with both anti-Ly5.1 antibody and EtBr to determine cell death in each population of cocultured DP thymocytes. Percent cell death was quantitated and normalized as described in Materials and Methods. (d) Schematic of the mechanism by which TCR-CD28 coengagement kills DP thymocytes. This figure illustrates two possible CD28-dependent mechanisms of TCR-mediated apoptosis of DP thymocytes, both of which result in death exclusively of TCR-CD28–stimulated DP thymocytes. The upper figure (i) illustrates one scenario in which simultaneous coengagement of TCR and CD28 molecules directly and cell-autonomously induces an apoptotic program. The lower figure (ii) illustrates an alternative scenario in which simultaneous coengagement of TCR and CD28 induces expression of a death domain containing receptor (Y) that signals apoptosis upon interaction with its ligand (Y-L, Y ligand) that is also expressed on DP thymocytes. In this latter case, the ligand could conceivably engage the death receptor in either cis or trans.