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Type I interferons keep activated T cells alive.

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

Bottom Line: 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.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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IFN-α/β do not stimulate the proliferation of activated T  cells. Lymph node T cells were purified from B10 mice primed 2 d previously with 150 μg/mouse SEB. The cells were cultured for 3 d in the  presence of the indicated concentrations of IFN-α/β or IL-2 and then  pulsed with [3H]TdR as described in Materials and Methods Results  shown are the mean ± geometric SE of triplicate cultures. Similar results  were obtained from cells tested after 2 d of culture.
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Figure 5: IFN-α/β do not stimulate the proliferation of activated T cells. Lymph node T cells were purified from B10 mice primed 2 d previously with 150 μg/mouse SEB. The cells were cultured for 3 d in the presence of the indicated concentrations of IFN-α/β or IL-2 and then pulsed with [3H]TdR as described in Materials and Methods Results shown are the mean ± geometric SE of triplicate cultures. Similar results were obtained from cells tested after 2 d of culture.

Mentions: IL-15 stimulates the proliferation of activated T cells but IFN-α/β do not (37–40). To confirm the idea that, in the experiments described in this paper, IFN-α/β were not acting via IL-15, we tested their effects on T cell proliferation. T cells were isolated from mice given SEB 2 d previously and cultured in the presence of different concentrations of IFN-α/β or as controls without added cytokines or with IL-2. The cells cultured alone did not proliferate. They divided vigorously in response to IL-2. Such cells also divided in response to IL-15 (data not shown). The cells did not divide at all in response to IFN-α/β (Fig. 5). The same conclusion was drawn from experiments in which T cells were labeled with CFSE and cultured in the presence or absence of IFN-α/β or IL-15. After 24 h, CFSE staining showed that, of the activated CD8+ T cells that were still alive, 8.9 ± 1.2% had divided if the cells were cultured alone, whereas 5.5 ± 0.6 or 15.5 ± 0.74% had divided if the cells were cultured in IFN-α/β or IL-15, respectively. Likewise, counts of total cell yield showed that there was no difference in the number of T cells per culture after 24 h of incubation in the presence or absence of IFN-α/β. In one experiment, 6.1 ± 0.5 × 105 cells were recovered from cultures incubated for 24 h without IFN-α/β, and 5.4 ± 0.3 × 105 cells were recovered from cultures incubated with 3,333 U/ml IFN-α/β. Hence, IFN-α/β do not cause activated T cells to divide.


Type I interferons keep activated T cells alive.

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

IFN-α/β do not stimulate the proliferation of activated T  cells. Lymph node T cells were purified from B10 mice primed 2 d previously with 150 μg/mouse SEB. The cells were cultured for 3 d in the  presence of the indicated concentrations of IFN-α/β or IL-2 and then  pulsed with [3H]TdR as described in Materials and Methods Results  shown are the mean ± geometric SE of triplicate cultures. Similar results  were obtained from cells tested after 2 d of culture.
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Related In: Results  -  Collection

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Figure 5: IFN-α/β do not stimulate the proliferation of activated T cells. Lymph node T cells were purified from B10 mice primed 2 d previously with 150 μg/mouse SEB. The cells were cultured for 3 d in the presence of the indicated concentrations of IFN-α/β or IL-2 and then pulsed with [3H]TdR as described in Materials and Methods Results shown are the mean ± geometric SE of triplicate cultures. Similar results were obtained from cells tested after 2 d of culture.
Mentions: IL-15 stimulates the proliferation of activated T cells but IFN-α/β do not (37–40). To confirm the idea that, in the experiments described in this paper, IFN-α/β were not acting via IL-15, we tested their effects on T cell proliferation. T cells were isolated from mice given SEB 2 d previously and cultured in the presence of different concentrations of IFN-α/β or as controls without added cytokines or with IL-2. The cells cultured alone did not proliferate. They divided vigorously in response to IL-2. Such cells also divided in response to IL-15 (data not shown). The cells did not divide at all in response to IFN-α/β (Fig. 5). The same conclusion was drawn from experiments in which T cells were labeled with CFSE and cultured in the presence or absence of IFN-α/β or IL-15. After 24 h, CFSE staining showed that, of the activated CD8+ T cells that were still alive, 8.9 ± 1.2% had divided if the cells were cultured alone, whereas 5.5 ± 0.6 or 15.5 ± 0.74% had divided if the cells were cultured in IFN-α/β or IL-15, respectively. Likewise, counts of total cell yield showed that there was no difference in the number of T cells per culture after 24 h of incubation in the presence or absence of IFN-α/β. In one experiment, 6.1 ± 0.5 × 105 cells were recovered from cultures incubated for 24 h without IFN-α/β, and 5.4 ± 0.3 × 105 cells were recovered from cultures incubated with 3,333 U/ml IFN-α/β. Hence, IFN-α/β do not cause activated T cells to divide.

Bottom Line: 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.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