Type I Interferon Protects Antiviral CD8+ T Cells from NK Cell Cytotoxicity

被引：185

作者：

Xu, Haifeng C. ^{[1
,2
]}

Grusdat, Melanie ^{[1
]}

Pandyra, Aleksandra A. ^{[2
]}

Polz, Robin ^{[1
]}

Huang, Jun ^{[1
]}

Sharma, Piyush ^{[2
]}

Deenen, Rene ^{[3
]}

Koehrer, Karl ^{[3
]}

Rahbar, Ramtin ^{[4
]}

Diefenbach, Andreas ^{[5
]}

Gibbert, Kathrin ^{[6
]}

Loehning, Max ^{[7
,8
]}

Hoecker, Lena ^{[9
]}

Waibler, Zoe ^{[9
]}

Haeussinger, Dieter ^{[1
]}

Mak, Tak W. ^{[4
]}

Ohashi, Pamela S. ^{[4
]}

Lang, Karl S. ^{[2
]}

Lang, Philipp A. ^{[1
]}

机构：

[1] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infect Dis, D-40225 Dusseldorf, Germany

[2] Univ Duisburg Essen, Fac Med, Inst Immunol, D-45147 Essen, Germany

[3] Univ Dusseldorf, Cluster Excellence Plant Sci CEPLAS, Biol & Med Res Ctr BMFZ, D-40225 Dusseldorf, Germany

[4] Univ Hlth Network UHN, Princess Margaret Canc Ctr, Campell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada

[5] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Med Microbiol & Hyg, D-55131 Mainz, Germany

[6] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, D-45147 Essen, Germany

[7] Charite, Dept Rheumatol & Clin Immunol, D-10117 Berlin, Germany

[8] German Rheumatism Res Ctr DRFZ, Leibniz Inst, D-10117 Berlin, Germany

[9] Paul Ehrlich Inst, D-63225 Langen, Germany

来源：

IMMUNITY | 2014年 / 40卷 / 06期

关键词：

NATURAL-KILLER-CELLS; PLASMACYTOID DENDRITIC CELLS; CHRONIC HEPATITIS-C; IMMUNE-RESPONSES; TRANSGENIC MICE; RECEPTOR; VIRUS; EFFECTOR; THERAPY; INNATE;

D O I：

10.1016/j.immuni.2014.05.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Despite development of new antiviral drugs, viral infections are still a major health problem. The most potent antiviral defense mechanism is the innate production of type I interferon (IFN-I), which not only limits virus replication but also promotes antiviral T cell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on T cells prevented their rapid elimination in vivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3(-/-)).The elimination of Ifnar1(-/-) T cells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of T cells against regulatory NK cell function.

引用

页码：949 / 960

页数：12

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