Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes.

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Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes. / Pongracz, Judit; Parnell, Sonia; Anderson, Graham; Jaffrézou, JP; Jenkinson, Eric.

In: Molecular immunology, Vol. 39, No. 16, 01.06.2003, p. 1013-23.

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@article{0c062ddb2bea4517b4f6fb9b4bdc581e,
title = "Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes.",
abstract = "While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).",
keywords = "thymocytes, Akt/PKB, Con A",
author = "Judit Pongracz and Sonia Parnell and Graham Anderson and JP Jaffr{\'e}zou and Eric Jenkinson",
year = "2003",
month = jun,
day = "1",
doi = "10.1016/S0161-5890(03)00044-0",
language = "English",
volume = "39",
pages = "1013--23",
journal = "Molecular immunology",
issn = "0161-5890",
publisher = "Elsevier",
number = "16",

}

RIS

TY - JOUR

T1 - Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes.

AU - Pongracz, Judit

AU - Parnell, Sonia

AU - Anderson, Graham

AU - Jaffrézou, JP

AU - Jenkinson, Eric

PY - 2003/6/1

Y1 - 2003/6/1

N2 - While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).

AB - While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).

KW - thymocytes

KW - Akt/PKB

KW - Con A

U2 - 10.1016/S0161-5890(03)00044-0

DO - 10.1016/S0161-5890(03)00044-0

M3 - Article

C2 - 12749908

VL - 39

SP - 1013

EP - 1023

JO - Molecular immunology

JF - Molecular immunology

SN - 0161-5890

IS - 16

ER -