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Type I interferons keep activated T cells alive.

Marrack P, Kappler J, Mitchell T - J. Exp. Med. (1999)

Bottom Line: It was due to direct effects of the IFNs on the T cells and was not mediated by induction of a second cytokine such as interleukin 15.IFN-alpha/beta did not raise the levels of Bcl-2 or Bcl-XL in T cells.Therefore, their activity was distinct from that of members of the interleukin 2 family or CD28 engagement.

View Article: PubMed Central - PubMed

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

ABSTRACT
Antigen injection into animals causes antigen-specific T cells to become activated and, rapidly thereafter, die. This antigen-induced death is inhibited by inflammation. To find out how inflammation has this effect, various cytokines were tested for their ability to interfere with the rapid death of activated T cells. T cells were activated in vivo, isolated, and cultured with the test reagents. Two groups of cytokines were active, members of the interleukin 2 family and the interferons (IFNs) alpha and beta. This activity of IFN-alpha/beta has not been described previously. It was due to direct effects of the IFNs on the T cells and was not mediated by induction of a second cytokine such as interleukin 15. IFN-gamma did not slow the death of activated T cells, and therefore the activity of IFN-alpha/beta was not mediated only by activation of Stat 1, a protein that is affected by both classes of IFN. IFN-alpha/beta did not raise the levels of Bcl-2 or Bcl-XL in T cells. Therefore, their activity was distinct from that of members of the interleukin 2 family or CD28 engagement. Since IFN-alpha/beta are very efficiently generated in response to viral and bacterial infections, these molecules may be among the signals that the immune system uses to prevent activated T cell death during infections.

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Activated and resting T cells bear receptors for IFN-α/β and  IFN-γ. Mice were primed and T cells were cultured as described in the  legend to Fig. 2. 20 h after the start of culture, the cells were isolated and  stained for Vβ8, Kb, and CD4 or CD8 as described in Materials and Methods. The results shown are the mean ± SE of triplicate cultures of staining  with anti-Kb antibody in arbitrary units based on staining intensities.
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Figure 3: Activated and resting T cells bear receptors for IFN-α/β and IFN-γ. Mice were primed and T cells were cultured as described in the legend to Fig. 2. 20 h after the start of culture, the cells were isolated and stained for Vβ8, Kb, and CD4 or CD8 as described in Materials and Methods. The results shown are the mean ± SE of triplicate cultures of staining with anti-Kb antibody in arbitrary units based on staining intensities.

Mentions: The fact that IFN-α/β have only a very slight effect on the rate of death of resting T cells was also demonstrated in an experiment in which IFN-α/β was titrated. Increasing doses of IFN-α/β had increasing abilities to promote the survival of activated T cells and had very little effect on the survival of resting T cells (Fig. 2). This was not due to absence of IFN-α/β receptors on resting T cells, since, as shown in Fig. 3, culture in IFN-α/β increased the levels of class I MHC on resting T cells. For CD4+ T cells, the effects of IFN-α/β on class I expression were less dramatic if the T cells were resting compared with if they were activated. On the other hand, for CD8+ T cells the dose– response curve was almost exactly the same whether or not the cells were activated.


Type I interferons keep activated T cells alive.

Marrack P, Kappler J, Mitchell T - J. Exp. Med. (1999)

Activated and resting T cells bear receptors for IFN-α/β and  IFN-γ. Mice were primed and T cells were cultured as described in the  legend to Fig. 2. 20 h after the start of culture, the cells were isolated and  stained for Vβ8, Kb, and CD4 or CD8 as described in Materials and Methods. The results shown are the mean ± SE of triplicate cultures of staining  with anti-Kb antibody in arbitrary units based on staining intensities.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192920&req=5

Figure 3: Activated and resting T cells bear receptors for IFN-α/β and IFN-γ. Mice were primed and T cells were cultured as described in the legend to Fig. 2. 20 h after the start of culture, the cells were isolated and stained for Vβ8, Kb, and CD4 or CD8 as described in Materials and Methods. The results shown are the mean ± SE of triplicate cultures of staining with anti-Kb antibody in arbitrary units based on staining intensities.
Mentions: The fact that IFN-α/β have only a very slight effect on the rate of death of resting T cells was also demonstrated in an experiment in which IFN-α/β was titrated. Increasing doses of IFN-α/β had increasing abilities to promote the survival of activated T cells and had very little effect on the survival of resting T cells (Fig. 2). This was not due to absence of IFN-α/β receptors on resting T cells, since, as shown in Fig. 3, culture in IFN-α/β increased the levels of class I MHC on resting T cells. For CD4+ T cells, the effects of IFN-α/β on class I expression were less dramatic if the T cells were resting compared with if they were activated. On the other hand, for CD8+ T cells the dose– response curve was almost exactly the same whether or not the cells were activated.

Bottom Line: It was due to direct effects of the IFNs on the T cells and was not mediated by induction of a second cytokine such as interleukin 15.IFN-alpha/beta did not raise the levels of Bcl-2 or Bcl-XL in T cells.Therefore, their activity was distinct from that of members of the interleukin 2 family or CD28 engagement.

View Article: PubMed Central - PubMed

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

ABSTRACT
Antigen injection into animals causes antigen-specific T cells to become activated and, rapidly thereafter, die. This antigen-induced death is inhibited by inflammation. To find out how inflammation has this effect, various cytokines were tested for their ability to interfere with the rapid death of activated T cells. T cells were activated in vivo, isolated, and cultured with the test reagents. Two groups of cytokines were active, members of the interleukin 2 family and the interferons (IFNs) alpha and beta. This activity of IFN-alpha/beta has not been described previously. It was due to direct effects of the IFNs on the T cells and was not mediated by induction of a second cytokine such as interleukin 15. IFN-gamma did not slow the death of activated T cells, and therefore the activity of IFN-alpha/beta was not mediated only by activation of Stat 1, a protein that is affected by both classes of IFN. IFN-alpha/beta did not raise the levels of Bcl-2 or Bcl-XL in T cells. Therefore, their activity was distinct from that of members of the interleukin 2 family or CD28 engagement. Since IFN-alpha/beta are very efficiently generated in response to viral and bacterial infections, these molecules may be among the signals that the immune system uses to prevent activated T cell death during infections.

Show MeSH
Related in: MedlinePlus