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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 transgenic T cells produce higher levels of IL-2 on stimulation with anti-CD3 antibody. T cells purified from the lymph nodes of  bad, bcl-2 transgenic mice, and nontransgenic mice were activated with  serial dilution of cross-linked anti-CD3 antibody. IL-2 production was  determined by CTLL assay and [3H]thymidine incorporation.
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Figure 9: bad transgenic T cells produce higher levels of IL-2 on stimulation with anti-CD3 antibody. T cells purified from the lymph nodes of bad, bcl-2 transgenic mice, and nontransgenic mice were activated with serial dilution of cross-linked anti-CD3 antibody. IL-2 production was determined by CTLL assay and [3H]thymidine incorporation.

Mentions: Activation of T cells is associated with their progression through the cell cycle. Activated T cells produced IL-2, which directly promotes cell cycle entry (46). Having observed that bad can promote cell cycle progression, we examined whether bad could affect the production of IL-2 in mature T cells after activation via anti-CD3. A precedent for this comes from studies on T cells from bcl-2 transgenic mice which show that bcl-2 overexpression significantly decreases IL-2 production (44). Therefore, we purified T cells from the lymph nodes of bad transgenic, bcl-2 transgenic, and nontransgenic mice, activated the T cells using serial dilutions of plate bound anti-CD3 antibody, and assayed the production of IL-2. The bcl-2 transgenic T cells produced much less IL-2 than those from nontransgenic mice, as reported previously (44). However, the bad transgenic T cells produced substantially more IL-2 than T cells from nontransgenic mice (Fig. 9). This effect on IL-2 production was not apparent after costimulation of purified bad transgenic T cells with anti-CD28 as well as serially diluted anti-CD3 antibody (data not shown). This may be due to the fact that anti-CD28 strongly induces bcl-xL expression (47), which would then bind the excess Bad present.


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 transgenic T cells produce higher levels of IL-2 on stimulation with anti-CD3 antibody. T cells purified from the lymph nodes of  bad, bcl-2 transgenic mice, and nontransgenic mice were activated with  serial dilution of cross-linked anti-CD3 antibody. IL-2 production was  determined by CTLL assay and [3H]thymidine incorporation.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: bad transgenic T cells produce higher levels of IL-2 on stimulation with anti-CD3 antibody. T cells purified from the lymph nodes of bad, bcl-2 transgenic mice, and nontransgenic mice were activated with serial dilution of cross-linked anti-CD3 antibody. IL-2 production was determined by CTLL assay and [3H]thymidine incorporation.
Mentions: Activation of T cells is associated with their progression through the cell cycle. Activated T cells produced IL-2, which directly promotes cell cycle entry (46). Having observed that bad can promote cell cycle progression, we examined whether bad could affect the production of IL-2 in mature T cells after activation via anti-CD3. A precedent for this comes from studies on T cells from bcl-2 transgenic mice which show that bcl-2 overexpression significantly decreases IL-2 production (44). Therefore, we purified T cells from the lymph nodes of bad transgenic, bcl-2 transgenic, and nontransgenic mice, activated the T cells using serial dilutions of plate bound anti-CD3 antibody, and assayed the production of IL-2. The bcl-2 transgenic T cells produced much less IL-2 than those from nontransgenic mice, as reported previously (44). However, the bad transgenic T cells produced substantially more IL-2 than T cells from nontransgenic mice (Fig. 9). This effect on IL-2 production was not apparent after costimulation of purified bad transgenic T cells with anti-CD28 as well as serially diluted anti-CD3 antibody (data not shown). This may be due to the fact that anti-CD28 strongly induces bcl-xL expression (47), which would then bind the excess Bad present.

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