Limits...
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.

Show MeSH

Related in: MedlinePlus

bad transgenic mice have decreased numbers of mature α/β T cells. (A) FACS®  analysis of CD4 vs. CD8 expression of thymocytes and (B) splenocytes from bad transgenic  and nontransgenic littermates. Cells were stained with specific anti-CD4 and anti-CD8 antibodies. The subpopulations of CD8+CD4+, CD4+CD8−, and CD4−CD8+ T cells are gated  and their percentages given. (C) Histogram indicating the percentage of TCR-γ/δ expressing cells within the CD4−CD8− thymocytes of bad transgenic and nontransgenic littermates.  The numbers in parentheses indicate the total number of TCR-γ/δ expressing cells in each  thymus.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2192908&req=5

Figure 3: bad transgenic mice have decreased numbers of mature α/β T cells. (A) FACS® analysis of CD4 vs. CD8 expression of thymocytes and (B) splenocytes from bad transgenic and nontransgenic littermates. Cells were stained with specific anti-CD4 and anti-CD8 antibodies. The subpopulations of CD8+CD4+, CD4+CD8−, and CD4−CD8+ T cells are gated and their percentages given. (C) Histogram indicating the percentage of TCR-γ/δ expressing cells within the CD4−CD8− thymocytes of bad transgenic and nontransgenic littermates. The numbers in parentheses indicate the total number of TCR-γ/δ expressing cells in each thymus.

Mentions: We analyzed the bad transgenic mice to look at the consequences of overexpressing bad within their T cells. In two independent lines of bad transgenic mice, bad line 1 and bad line 3, the transgenic mice have greatly reduced numbers of thymocytes, up to 10-fold less, in comparison with nontransgenic littermates (Table I). Similarly, the numbers of mature T cells in the spleen are also significantly reduced in bad transgenic mice (data not shown). We then analyzed the effect of bad on the different populations of T cells in the thymus. Bad transgenic mice have greatly decreased percentages of both CD4−CD8+ and CD4+CD8− T cells compared to nontransgenic mice (Fig. 3 A). Similar analysis of splenocytes shows a substantial decrease in the proportion of mature single positive (SP) T cells present in the bad transgenic mice compared to controls (Fig. 3 B). Unlike for TCR-α/β T cells, the significance of apoptosis in TCR-γ/δ T cell development is unknown. We found that the percentage of γ/δ T cells relative to the percentage of α/β T cells in the CD4−CD8− thymocytes of bad transgenic mice was virtually unchanged relative to nontransgenic thymuses (Fig. 3 C). Similarly, the total number of TCR-γ/δ expressing cells in the thymus of bad transgenic mice is not significantly different. Therefore, the effect of the bad transgene on mature T cell production is restricted to TCR-α/β bearing T cells rather than TCR-γ/δ T cells.


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 mice have decreased numbers of mature α/β T cells. (A) FACS®  analysis of CD4 vs. CD8 expression of thymocytes and (B) splenocytes from bad transgenic  and nontransgenic littermates. Cells were stained with specific anti-CD4 and anti-CD8 antibodies. The subpopulations of CD8+CD4+, CD4+CD8−, and CD4−CD8+ T cells are gated  and their percentages given. (C) Histogram indicating the percentage of TCR-γ/δ expressing cells within the CD4−CD8− thymocytes of bad transgenic and nontransgenic littermates.  The numbers in parentheses indicate the total number of TCR-γ/δ expressing cells in each  thymus.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: bad transgenic mice have decreased numbers of mature α/β T cells. (A) FACS® analysis of CD4 vs. CD8 expression of thymocytes and (B) splenocytes from bad transgenic and nontransgenic littermates. Cells were stained with specific anti-CD4 and anti-CD8 antibodies. The subpopulations of CD8+CD4+, CD4+CD8−, and CD4−CD8+ T cells are gated and their percentages given. (C) Histogram indicating the percentage of TCR-γ/δ expressing cells within the CD4−CD8− thymocytes of bad transgenic and nontransgenic littermates. The numbers in parentheses indicate the total number of TCR-γ/δ expressing cells in each thymus.
Mentions: We analyzed the bad transgenic mice to look at the consequences of overexpressing bad within their T cells. In two independent lines of bad transgenic mice, bad line 1 and bad line 3, the transgenic mice have greatly reduced numbers of thymocytes, up to 10-fold less, in comparison with nontransgenic littermates (Table I). Similarly, the numbers of mature T cells in the spleen are also significantly reduced in bad transgenic mice (data not shown). We then analyzed the effect of bad on the different populations of T cells in the thymus. Bad transgenic mice have greatly decreased percentages of both CD4−CD8+ and CD4+CD8− T cells compared to nontransgenic mice (Fig. 3 A). Similar analysis of splenocytes shows a substantial decrease in the proportion of mature single positive (SP) T cells present in the bad transgenic mice compared to controls (Fig. 3 B). Unlike for TCR-α/β T cells, the significance of apoptosis in TCR-γ/δ T cell development is unknown. We found that the percentage of γ/δ T cells relative to the percentage of α/β T cells in the CD4−CD8− thymocytes of bad transgenic mice was virtually unchanged relative to nontransgenic thymuses (Fig. 3 C). Similarly, the total number of TCR-γ/δ expressing cells in the thymus of bad transgenic mice is not significantly different. Therefore, the effect of the bad transgene on mature T cell production is restricted to TCR-α/β bearing T cells rather than TCR-γ/δ T cells.

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