T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)-mediated, activation-induced cell death upon restimulation with antigen. Unequal apoptosis is also observed without restimulation, after a longer lag period. Both effectors undergo delayed apoptosis induced by a non–Fas-mediated pathway. When Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially, suggesting the responsible factor(s) is intrinsic to each population. Both Th1 and Th2 effectors express Fas and FasL, but only Th2 effectors express high levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas signaling. The rapid death of Th1 effectors leading to selective Th2 survival provides a novel mechanism for differential regulation of the two subsets.
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19 May 1997
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May 19 1997
Unequal Death in T Helper Cell (Th)1 and Th2 Effectors: Th1, but not Th2, Effectors Undergo Rapid Fas/FasL-mediated Apoptosis
Xiaohong Zhang,
Xiaohong Zhang
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Thomas Brunner,
Thomas Brunner
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Laura Carter,
Laura Carter
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Richard W. Dutton,
Richard W. Dutton
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Paul Rogers,
Paul Rogers
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Linda Bradley,
Linda Bradley
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Takaaki Sato,
Takaaki Sato
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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John C. Reed,
John C. Reed
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Douglas Green,
Douglas Green
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Susan L. Swain
Susan L. Swain
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
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Xiaohong Zhang
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Thomas Brunner
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Laura Carter
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Richard W. Dutton
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Paul Rogers
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Linda Bradley
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Takaaki Sato
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
John C. Reed
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Douglas Green
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Susan L. Swain
From the *University of California, San Diego, La Jolla, California 92093; ‡La Jolla Institute of Allergy and Immunology, San Diego, California 92121; §The Burnham Institute, La Jolla, California 92037; and ‖Trudeau Institute, Saranac Lake, New York 12983
Address correspondence to Susan L. Swain, Trudeau Institute, PO Box 59, 100 Algonquin Ave., Saranac Lake, NY 12983. The present address of T. Sato is Columbia University, New York, NY 10027. The present address of L. Bradley and X. Zhang is Scripps Research Institute, La Jolla, CA 92032. The present address of P. Rogers is La Jolla Institute of Allergy and Immunology, San Diego, CA 92121.
The authors are thankful to S. Nagata and P. Golstein for providing valuable reagents.
This research was supported by National Institutes of Health grants AI37935 and AI26887 to S.L. Swain, GM52735 to D.R. Green, CA72994 and ACS IM414 to J.C. Reed, and a fellowship from the U.S. Army Breast Cancer Program to T. Sato. T. Brunner is a fellow of the Swiss Society for Med. Biol. Fellowships.
1Abbreviations used in this paper: AICD, activation-induced cell death; CFSE, 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester; FasL, Fas ligand; ICAM, intracellular adhesion molecule; FAP-1, Fas-associated phosphatase 1; FL, fluorescein; mRNA, messenger RNA; PCCF, pigeon cytochrome c fragment 88-104; RPA, RNase protection assay; TdT, terminal deoxynucleotidyl transferase; Tg, transgenic.
X. Zhang and T. Brunner contributed equally to this work.
Received:
September 18 1996
Revision Received:
March 11 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (10): 1837–1849.
Article history
Received:
September 18 1996
Revision Received:
March 11 1997
Citation
Xiaohong Zhang, Thomas Brunner, Laura Carter, Richard W. Dutton, Paul Rogers, Linda Bradley, Takaaki Sato, John C. Reed, Douglas Green, Susan L. Swain; Unequal Death in T Helper Cell (Th)1 and Th2 Effectors: Th1, but not Th2, Effectors Undergo Rapid Fas/FasL-mediated Apoptosis. J Exp Med 19 May 1997; 185 (10): 1837–1849. doi: https://doi.org/10.1084/jem.185.10.1837
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