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) α and β. This activity of IFN-α/β 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-γ did not slow the death of activated T cells, and therefore the activity of IFN-α/β was not mediated only by activation of Stat 1, a protein that is affected by both classes of IFN. IFN-α/β 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-α/β 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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1 February 1999
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February 01 1999
Type I Interferons Keep Activated T Cells Alive
Philippa Marrack,
Philippa Marrack
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
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John Kappler,
John Kappler
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
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Tom Mitchell
Tom Mitchell
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
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Philippa Marrack
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
John Kappler
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
Tom Mitchell
From the *Howard Hughes Medical Institute, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206; and the ‡Department of Biochemistry Biophysics and Genetics, the §Department of Immunology, the ‖Department of Pharmacology, and the ¶Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
Address correspondence to Philippa Marrack, Howard Hughes Medical Institute, National Jewish Medical and Research Center, Goodman Bldg., 5th Floor, 1400 Jackson St., Denver, CO 80206. Phone: 303-398-1322; Fax: 303-398-1396; E-mail: [email protected]
1
Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; CY, cychrome; SEB, staphylococcal enterotoxin B.
Received:
August 17 1998
Revision Received:
October 14 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (3): 521–530.
Article history
Received:
August 17 1998
Revision Received:
October 14 1998
Citation
Philippa Marrack, John Kappler, Tom Mitchell; Type I Interferons Keep Activated T Cells Alive . J Exp Med 1 February 1999; 189 (3): 521–530. doi: https://doi.org/10.1084/jem.189.3.521
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