共 65 条
Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo
被引:222
作者:

Tinoco, Roberto
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

Alcalde, Victor
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h-index: 0
机构:
Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

Yang, Yating
论文数: 0 引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

Sauer, Karsten
论文数: 0 引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

Zuniga, Elina I.
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h-index: 0
机构:
Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
机构:
[1] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
[2] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
来源:
基金:
美国国家卫生研究院;
关键词:
HEPATITIS-C-VIRUS;
LYMPHOCYTIC CHORIOMENINGITIS VIRUS;
HUMAN-IMMUNODEFICIENCY-VIRUS;
PLASMACYTOID DENDRITIC CELLS;
NATURAL-KILLER-CELL;
TGF-BETA;
INTERLEUKIN-10;
RECEPTOR;
IMMUNE-RESPONSES;
PD-1;
EXPRESSION;
B-VIRUS;
D O I:
10.1016/j.immuni.2009.06.015
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Although deficient CD8(+) T cell responses have long been associated with chronic viral infections, the underlying mechanisms are still unclear. Here we report that sustained transforming growth factor-beta (TGF-beta) expression and phosphorylation of its signaling mediator, Smad-2, Were distinctive features of virus-specific CD8(+) T cells during chronic versus acute viral infections in vivo. The result was TGF-beta-dependent apoptosis of virus-specific CD8(+) T cells that related to upregulation of the proapoptotic protein Bim during chronic infection. Moreover, selective attenuation of TGF-beta signaling in T cells increased the numbers and multiple functions of antiviral CD8(+) T cells and enabled rapid eradication of the persistence-prone virus and memory generation. Finally, we found that cell-intrinsic TGF-beta signaling was responsible for virus-specific-CD8(+) T cell apoptosis and decreased numbers but was not necessary for their functional exhaustion. Our findings reveal persisting TGF-beta-Smad signaling as a hallmark and key regulator of CD8(+) T cell responses during chronic viral infections in vivo.
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页码:145 / 157
页数:13
相关论文
共 65 条
[1]
T4+ T-HELPER CELL-FUNCTION INVIVO - DIFFERENTIAL REQUIREMENT FOR INDUCTION OF ANTIVIRAL CYTO-TOXIC T-CELL AND ANTIBODY-RESPONSES
[J].
AHMED, R
;
BUTLER, LD
;
BHATTI, L
.
JOURNAL OF VIROLOGY,
1988, 62 (06)
:2102-2106

AHMED, R
论文数: 0 引用数: 0
h-index: 0
机构:
ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285 ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285

BUTLER, LD
论文数: 0 引用数: 0
h-index: 0
机构:
ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285 ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285

BHATTI, L
论文数: 0 引用数: 0
h-index: 0
机构:
ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285 ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285
[2]
SELECTION OF GENETIC-VARIANTS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN SPLEENS OF PERSISTENTLY INFECTED MICE - ROLE IN SUPPRESSION OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE AND VIRAL PERSISTENCE
[J].
AHMED, R
;
SALMI, A
;
BUTLER, LD
;
CHILLER, JM
;
OLDSTONE, MBA
.
JOURNAL OF EXPERIMENTAL MEDICINE,
1984, 160 (02)
:521-540

AHMED, R
论文数: 0 引用数: 0
h-index: 0

SALMI, A
论文数: 0 引用数: 0
h-index: 0

BUTLER, LD
论文数: 0 引用数: 0
h-index: 0

CHILLER, JM
论文数: 0 引用数: 0
h-index: 0

OLDSTONE, MBA
论文数: 0 引用数: 0
h-index: 0
[3]
Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor β that can suppress HCV-specific T-cell responses
[J].
Alatrakchi, Nadia
;
Graham, Camilla S.
;
van der Vliet, Hans J. J.
;
Sherman, Kenneth E.
;
Exley, Mark A.
;
Koziel, Margaret James
.
JOURNAL OF VIROLOGY,
2007, 81 (11)
:5882-5892

Alatrakchi, Nadia
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

Graham, Camilla S.
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

van der Vliet, Hans J. J.
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

Sherman, Kenneth E.
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

Exley, Mark A.
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

Koziel, Margaret James
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[4]
Making sense of latent TGFβ activation
[J].
Annes, JP
;
Munger, JS
;
Rifkin, DB
.
JOURNAL OF CELL SCIENCE,
2003, 116 (02)
:217-224

Annes, JP
论文数: 0 引用数: 0
h-index: 0
机构: NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

Munger, JS
论文数: 0 引用数: 0
h-index: 0
机构: NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

Rifkin, DB
论文数: 0 引用数: 0
h-index: 0
机构: NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA
[5]
Restoring function in exhausted CD8 T cells during chronic viral infection
[J].
Barber, DL
;
Wherry, EJ
;
Masopust, D
;
Zhu, BG
;
Allison, JP
;
Sharpe, AH
;
Freeman, GJ
;
Ahmed, R
.
NATURE,
2006, 439 (7077)
:682-687

Barber, DL
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Wherry, EJ
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Masopust, D
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Zhu, BG
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Allison, JP
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Sharpe, AH
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Freeman, GJ
论文数: 0 引用数: 0
h-index: 0
机构: Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

Ahmed, R
论文数: 0 引用数: 0
h-index: 0
机构:
Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[6]
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
[J].
Betts, Michael R.
;
Nason, Martha C.
;
West, Sadie M.
;
De Rosa, Stephen C.
;
Migueles, Stephen A.
;
Abraham, Jonathan
;
Lederman, Michael M.
;
Benito, Jose M.
;
Goepfert, Paul A.
;
Connors, Mark
;
Roederer, Mario
;
Koup, Richard A.
.
BLOOD,
2006, 107 (12)
:4781-4789

Betts, Michael R.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Nason, Martha C.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

West, Sadie M.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

De Rosa, Stephen C.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Migueles, Stephen A.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Abraham, Jonathan
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Lederman, Michael M.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Benito, Jose M.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Goepfert, Paul A.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Connors, Mark
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Roederer, Mario
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

Koup, Richard A.
论文数: 0 引用数: 0
h-index: 0
机构: NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[7]
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
[J].
Blackburn, Shawn D.
;
Shin, Haina
;
Haining, W. Nicholas
;
Zou, Tao
;
Workman, Creg J.
;
Polley, Antonio
;
Betts, Michael R.
;
Freeman, Gordon J.
;
Vignali, Dario A. A.
;
Wherry, E. John
.
NATURE IMMUNOLOGY,
2009, 10 (01)
:29-37

Blackburn, Shawn D.
论文数: 0 引用数: 0
h-index: 0
机构:
Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Shin, Haina
论文数: 0 引用数: 0
h-index: 0
机构:
Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Haining, W. Nicholas
论文数: 0 引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Zou, Tao
论文数: 0 引用数: 0
h-index: 0
机构:
Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Workman, Creg J.
论文数: 0 引用数: 0
h-index: 0
机构:
St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Polley, Antonio
论文数: 0 引用数: 0
h-index: 0
机构:
Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Betts, Michael R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Freeman, Gordon J.
论文数: 0 引用数: 0
h-index: 0
机构:
Dana Farber Canc Inst, Boston, MA 02115 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Vignali, Dario A. A.
论文数: 0 引用数: 0
h-index: 0
机构:
St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA

Wherry, E. John
论文数: 0 引用数: 0
h-index: 0
机构:
Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
Wistar Inst Anat & Biol, Wistar Vaccine Ctr, Philadelphia, PA 19104 USA Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA
[8]
Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection
[J].
Boni, Carolina
;
Fisicaro, Paola
;
Valdatta, Caterina
;
Amadei, Barbara
;
Di Vincenzo, Paola
;
Giuberti, Tiziana
;
Laccabue, Diletta
;
Zerbini, Alessandro
;
Cavalli, Albertina
;
Missale, Gabriele
;
Bertoletti, Antonio
;
Ferrari, Carlo
.
JOURNAL OF VIROLOGY,
2007, 81 (08)
:4215-4225

论文数: 引用数:
h-index:
机构:

论文数: 引用数:
h-index:
机构:

Valdatta, Caterina
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

Amadei, Barbara
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

Di Vincenzo, Paola
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

Giuberti, Tiziana
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

Laccabue, Diletta
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

论文数: 引用数:
h-index:
机构:

Cavalli, Albertina
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

论文数: 引用数:
h-index:
机构:

Bertoletti, Antonio
论文数: 0 引用数: 0
h-index: 0
机构: Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, Lab Immunopatol Virale, I-43100 Parma, Italy

论文数: 引用数:
h-index:
机构:
[9]
VIRUS-INDUCED IMMUNOSUPPRESSION - IMMUNE SYSTEM-MEDIATED DESTRUCTION OF VIRUS-INFECTED DENDRITIC CELLS RESULTS IN GENERALIZED IMMUNE SUPPRESSION
[J].
BORROW, P
;
EVANS, CF
;
OLDSTONE, MBA
.
JOURNAL OF VIROLOGY,
1995, 69 (02)
:1059-1070

BORROW, P
论文数: 0 引用数: 0
h-index: 0

EVANS, CF
论文数: 0 引用数: 0
h-index: 0

OLDSTONE, MBA
论文数: 0 引用数: 0
h-index: 0
[10]
Interleukin-10 determines viral clearance or persistence in vivo
[J].
Brooks, David G.
;
Trifilo, Matthew J.
;
Edelmann, Kurt H.
;
Teyton, Luc
;
McGavern, Dorian B.
;
Oldstone, Michael B. A.
.
NATURE MEDICINE,
2006, 12 (11)
:1301-1309

Brooks, David G.
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

Trifilo, Matthew J.
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

Edelmann, Kurt H.
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

Teyton, Luc
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

McGavern, Dorian B.
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

Oldstone, Michael B. A.
论文数: 0 引用数: 0
h-index: 0
机构: Scripps Res Inst, Viral Immunobiol Lab, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA