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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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Resting T cells die in culture. This death is inhibited by culture with IL-4 or IL-7. Resting lymph node T cells from AD10 TCR  transgenic mice were cultured at 2 × 105 cells/well with or without 100  U/ml of IL-4 or IL-7 for 24 and 48 h. Before culture, <5% of the cells  contained <2 N DNA. After culture, cells were stained with propidum  iodide and analyzed by flow cytometry to determine DNA content. The  number given in each histogram is the percent of T cells that were apoptotic as defined by DNA content. Results shown are typical of three independent experiments.
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Figure 1: Resting T cells die in culture. This death is inhibited by culture with IL-4 or IL-7. Resting lymph node T cells from AD10 TCR transgenic mice were cultured at 2 × 105 cells/well with or without 100 U/ml of IL-4 or IL-7 for 24 and 48 h. Before culture, <5% of the cells contained <2 N DNA. After culture, cells were stained with propidum iodide and analyzed by flow cytometry to determine DNA content. The number given in each histogram is the percent of T cells that were apoptotic as defined by DNA content. Results shown are typical of three independent experiments.

Mentions: Sample data from such an experiment are shown in Fig. 1. Before culture less than 5% of the cells were dead. However, 24 and 48 h later 50 and 77%, of the cells had died respectively.


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)

Resting T cells die in culture. This death is inhibited by culture with IL-4 or IL-7. Resting lymph node T cells from AD10 TCR  transgenic mice were cultured at 2 × 105 cells/well with or without 100  U/ml of IL-4 or IL-7 for 24 and 48 h. Before culture, <5% of the cells  contained <2 N DNA. After culture, cells were stained with propidum  iodide and analyzed by flow cytometry to determine DNA content. The  number given in each histogram is the percent of T cells that were apoptotic as defined by DNA content. Results shown are typical of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198981&req=5

Figure 1: Resting T cells die in culture. This death is inhibited by culture with IL-4 or IL-7. Resting lymph node T cells from AD10 TCR transgenic mice were cultured at 2 × 105 cells/well with or without 100 U/ml of IL-4 or IL-7 for 24 and 48 h. Before culture, <5% of the cells contained <2 N DNA. After culture, cells were stained with propidum iodide and analyzed by flow cytometry to determine DNA content. The number given in each histogram is the percent of T cells that were apoptotic as defined by DNA content. Results shown are typical of three independent experiments.
Mentions: Sample data from such an experiment are shown in Fig. 1. Before culture less than 5% of the cells were dead. However, 24 and 48 h later 50 and 77%, of the cells had died respectively.

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