Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity

被引：257

作者：

Lang, Philipp A. ^{[1
,2
,3
]}

Lang, Karl S. ^{[2
,4
]}

Xu, Haifeng C. ^{[1
,3
]}

Grusdat, Melanie ^{[2
]}

Parish, Ian A. ^{[5
]}

Recher, Mike ^{[6
]}

Elford, Alisha R. ^{[1
]}

Dhanji, Salim ^{[1
]}

Shaabani, Namir ^{[2
]}

Tran, Charles W. ^{[1
,3
]}

Dissanayake, Dilan ^{[1
,3
]}

Rahbar, Ramtin ^{[1
,3
]}

Ghazarian, Magar ^{[1
]}

Bruestle, Anne ^{[1
]}

Fine, Jason ^{[3
]}

Chen, Peter ^{[3
]}

Weaver, Casey T. ^{[7
]}

Klose, Christoph ^{[8
]}

Diefenbach, Andreas ^{[8
]}

Haeussinger, Dieter ^{[2
]}

Carlyle, James R. ^{[3
]}

Kaech, Susan M. ^{[5
,9
]}

Mak, Tak W. ^{[1
,3
,10
]}

Ohashi, Pamela S. ^{[1
,3
,10
]}

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada

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

[3] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[4] Univ Essen Gesamthsch, Inst Immunol, D-45147 Essen, Germany

[5] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

[6] Harvard Univ, Childrens Hosp, Div Immunol, Sch Med, Boston, MA 02115 USA

[7] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[8] Univ Freiburg, Inst Med Microbiol & Hyg, Med Ctr, D-79104 Freiburg, Germany

[9] Yale Univ, Howard Hughes Med Inst, Sch Med, New Haven, CT 06520 USA

[10] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

virus persistence; effector T cells; virus elimination; NK cell activation; regulatory innate immunity; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HEPATITIS-C VIRUS; NK CELLS; NKG2D RECEPTOR; INHIBITORY RECEPTOR; VIRAL PERSISTENCE; DEPENDENT MANNER; DENDRITIC CELLS; IN-VIVO; MICE;

D O I：

10.1073/pnas.1118834109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease. Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3(-/-), E4BP4(-/-)) mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILE-infected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore, we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.

引用

页码：1210 / 1215

页数：6

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