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Bad can act as a key regulator of T cell apoptosis and T cell development.

Mok CL, Gil-Gómez G, Williams O, Coles M, Taga S, Tolaini M, Norton T, Kioussis D, Brady HJ - J. Exp. Med. (1999)

Bottom Line: Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis.The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed.These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Immunology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom.

ABSTRACT
Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis. We generated bad transgenic mice to study the action of upregulated Bad expression on T cell apoptosis. The T cells from these mice are highly sensitive to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed. We show that the proapoptotic function of Bad in primary T cells is regulated by Akt kinase and that Bad overexpression enhances both cell cycle progression and interleukin 2 production after T cell activation. These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.

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bad transgene. (A) The mouse bad cDNA including a 5′ HA  epitope was cloned into the EcoRI site of the human CD2 VA expression  vector. The SalI-XbaI fragment was then isolated for microinjection.  Western blot analysis of transgene expression in the two transgenic lines  studied was carried out using total cell extract of thymocytes. Equal  amounts of protein were loaded in each lane. (B) The blot was probed  with the 12CA5 mAb against HA, to detect the presence of the transgene  and (C) with a polyclonal anti-Bad antibody to compare the levels of endogenous and transgenic Bad expression.
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Figure 2: bad transgene. (A) The mouse bad cDNA including a 5′ HA epitope was cloned into the EcoRI site of the human CD2 VA expression vector. The SalI-XbaI fragment was then isolated for microinjection. Western blot analysis of transgene expression in the two transgenic lines studied was carried out using total cell extract of thymocytes. Equal amounts of protein were loaded in each lane. (B) The blot was probed with the 12CA5 mAb against HA, to detect the presence of the transgene and (C) with a polyclonal anti-Bad antibody to compare the levels of endogenous and transgenic Bad expression.

Mentions: Mice were generated bearing a transgene with the mouse bad cDNA linked to a HA epitope under the control of the human CD2 promoter and locus control region (LCR) (Fig. 2 A). The bad transgene is targeted to the T cell lineage in both thymus and periphery (30, 31). The HA-tagged Bad protein produced by the transgene can be distinguished from the endogenous Bad protein using the mAb 12CA5 (32).


Bad can act as a key regulator of T cell apoptosis and T cell development.

Mok CL, Gil-Gómez G, Williams O, Coles M, Taga S, Tolaini M, Norton T, Kioussis D, Brady HJ - J. Exp. Med. (1999)

bad transgene. (A) The mouse bad cDNA including a 5′ HA  epitope was cloned into the EcoRI site of the human CD2 VA expression  vector. The SalI-XbaI fragment was then isolated for microinjection.  Western blot analysis of transgene expression in the two transgenic lines  studied was carried out using total cell extract of thymocytes. Equal  amounts of protein were loaded in each lane. (B) The blot was probed  with the 12CA5 mAb against HA, to detect the presence of the transgene  and (C) with a polyclonal anti-Bad antibody to compare the levels of endogenous and transgenic Bad expression.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192908&req=5

Figure 2: bad transgene. (A) The mouse bad cDNA including a 5′ HA epitope was cloned into the EcoRI site of the human CD2 VA expression vector. The SalI-XbaI fragment was then isolated for microinjection. Western blot analysis of transgene expression in the two transgenic lines studied was carried out using total cell extract of thymocytes. Equal amounts of protein were loaded in each lane. (B) The blot was probed with the 12CA5 mAb against HA, to detect the presence of the transgene and (C) with a polyclonal anti-Bad antibody to compare the levels of endogenous and transgenic Bad expression.
Mentions: Mice were generated bearing a transgene with the mouse bad cDNA linked to a HA epitope under the control of the human CD2 promoter and locus control region (LCR) (Fig. 2 A). The bad transgene is targeted to the T cell lineage in both thymus and periphery (30, 31). The HA-tagged Bad protein produced by the transgene can be distinguished from the endogenous Bad protein using the mAb 12CA5 (32).

Bottom Line: Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis.The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed.These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Immunology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom.

ABSTRACT
Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis. We generated bad transgenic mice to study the action of upregulated Bad expression on T cell apoptosis. The T cells from these mice are highly sensitive to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed. We show that the proapoptotic function of Bad in primary T cells is regulated by Akt kinase and that Bad overexpression enhances both cell cycle progression and interleukin 2 production after T cell activation. These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.

Show MeSH
Related in: MedlinePlus