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Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4.

Vella A, Teague TK, Ihle J, Kappler J, Marrack P - J. Exp. Med. (1997)

Bottom Line: Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival.Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner.These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

ABSTRACT
Although much is known about the activation, proliferation, and function of CD4(+) T cells, little is known about how they survive as resting T cells in animals. Resting T cells have a half-life in animals of more than a week; however, when they are removed from animals and placed in tissue culture their half-life falls to approximately 24 h. In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7). They may do this in part by maintaining levels of survival-promoting proteins such as Bcl-2 in the cells, because the levels of Bcl-2 and Bcl-Xl in resting T cells fall rapidly after the cells are isolated from animals, and are maintained by culture in IL-4. Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival. Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner. These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.

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IL-4 blocks the death of resting T cells that lack Stat6. (a) Prevention of resting T cell death by IL-4 is only slightly affected by lack of Stat6  in the T cell. T cells from normal or Stat6−/− mice were purified and cultured at 1.2 × 105 cells/well with various concentrations of IL-4. 42 h later, cells  were harvested and assayed for dead cells using propidium iodide staining. Open symbols, T cells from normal mice; closed symbols, T cells from Stat6−/−  mice. (b) Induction of class II is affected by lack of Stat6 in B cells. Spleen cells from normal or Stat6−/− mice were cultured at 3 × 105 cells/well with  various concentrations of IL-4. 42 h later, the cells were harvested and stained with FITC–anti-IAb α chain and phycoerythrin-labeled anti-B220. Data  shown are the mean anti-IAb fluorescences after gating on the B220 positive cells. Open symbols, B cells from normal mice; closed symbols, B cells from  Stat6−/− mice.
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Figure 4: IL-4 blocks the death of resting T cells that lack Stat6. (a) Prevention of resting T cell death by IL-4 is only slightly affected by lack of Stat6 in the T cell. T cells from normal or Stat6−/− mice were purified and cultured at 1.2 × 105 cells/well with various concentrations of IL-4. 42 h later, cells were harvested and assayed for dead cells using propidium iodide staining. Open symbols, T cells from normal mice; closed symbols, T cells from Stat6−/− mice. (b) Induction of class II is affected by lack of Stat6 in B cells. Spleen cells from normal or Stat6−/− mice were cultured at 3 × 105 cells/well with various concentrations of IL-4. 42 h later, the cells were harvested and stained with FITC–anti-IAb α chain and phycoerythrin-labeled anti-B220. Data shown are the mean anti-IAb fluorescences after gating on the B220 positive cells. Open symbols, B cells from normal mice; closed symbols, B cells from Stat6−/− mice.

Mentions: To test this, we compared the effects of IL-4 on the survival of resting T cells from Stat6-deficient (Stat6−/−) and normal mice (17, 18). The results are shown in Fig. 4 a. In the absence of added cytokines, T cells from Stat6−/− mice, like those from normal animals, died in culture. Increasing doses of IL-4 prevented the death of T cells from both types of animals. The sensitivity of the two types of cells to IL-4 was slightly different, with the Stat6−/− cells requiring between two- and fivefold more IL-4 than normal T cells for half-maximal rescue.


Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4.

Vella A, Teague TK, Ihle J, Kappler J, Marrack P - J. Exp. Med. (1997)

IL-4 blocks the death of resting T cells that lack Stat6. (a) Prevention of resting T cell death by IL-4 is only slightly affected by lack of Stat6  in the T cell. T cells from normal or Stat6−/− mice were purified and cultured at 1.2 × 105 cells/well with various concentrations of IL-4. 42 h later, cells  were harvested and assayed for dead cells using propidium iodide staining. Open symbols, T cells from normal mice; closed symbols, T cells from Stat6−/−  mice. (b) Induction of class II is affected by lack of Stat6 in B cells. Spleen cells from normal or Stat6−/− mice were cultured at 3 × 105 cells/well with  various concentrations of IL-4. 42 h later, the cells were harvested and stained with FITC–anti-IAb α chain and phycoerythrin-labeled anti-B220. Data  shown are the mean anti-IAb fluorescences after gating on the B220 positive cells. Open symbols, B cells from normal mice; closed symbols, B cells from  Stat6−/− mice.
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Related In: Results  -  Collection

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Figure 4: IL-4 blocks the death of resting T cells that lack Stat6. (a) Prevention of resting T cell death by IL-4 is only slightly affected by lack of Stat6 in the T cell. T cells from normal or Stat6−/− mice were purified and cultured at 1.2 × 105 cells/well with various concentrations of IL-4. 42 h later, cells were harvested and assayed for dead cells using propidium iodide staining. Open symbols, T cells from normal mice; closed symbols, T cells from Stat6−/− mice. (b) Induction of class II is affected by lack of Stat6 in B cells. Spleen cells from normal or Stat6−/− mice were cultured at 3 × 105 cells/well with various concentrations of IL-4. 42 h later, the cells were harvested and stained with FITC–anti-IAb α chain and phycoerythrin-labeled anti-B220. Data shown are the mean anti-IAb fluorescences after gating on the B220 positive cells. Open symbols, B cells from normal mice; closed symbols, B cells from Stat6−/− mice.
Mentions: To test this, we compared the effects of IL-4 on the survival of resting T cells from Stat6-deficient (Stat6−/−) and normal mice (17, 18). The results are shown in Fig. 4 a. In the absence of added cytokines, T cells from Stat6−/− mice, like those from normal animals, died in culture. Increasing doses of IL-4 prevented the death of T cells from both types of animals. The sensitivity of the two types of cells to IL-4 was slightly different, with the Stat6−/− cells requiring between two- and fivefold more IL-4 than normal T cells for half-maximal rescue.

Bottom Line: Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival.Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner.These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

ABSTRACT
Although much is known about the activation, proliferation, and function of CD4(+) T cells, little is known about how they survive as resting T cells in animals. Resting T cells have a half-life in animals of more than a week; however, when they are removed from animals and placed in tissue culture their half-life falls to approximately 24 h. In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7). They may do this in part by maintaining levels of survival-promoting proteins such as Bcl-2 in the cells, because the levels of Bcl-2 and Bcl-Xl in resting T cells fall rapidly after the cells are isolated from animals, and are maintained by culture in IL-4. Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival. Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner. These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.

Show MeSH
Related in: MedlinePlus