The Role of Heterotypic DENV-specific CD8+ T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection

被引：17

作者：

Talarico, Laura B. ^{[1
,2
]}

Batalle, Juan P. ^{[1
]}

Byrne, Alana B. ^{[1
,2
]}

Brahamian, Jorge M. ^{[1
]}

Ferretti, Adrian ^{[1
]}

Garcia, Ayelen G. ^{[1
]}

Mauri, Aldana ^{[1
]}

Simonetto, Carla ^{[1
]}

Hijano, Diego R. ^{[1
,3
]}

Lawrence, Andrea ^{[3
]}

Acosta, Patricio L. ^{[1
,2
]}

Caballero, Mauricio T. ^{[1
]}

Paredes Rojas, Yesica ^{[2
,4
]}

Ibanez, Lorena I. ^{[2
,4
]}

Melendi, Guillermina A. ^{[1
]}

Rey, Felix A. ^{[5
]}

Damonte, Elsa B. ^{[6
]}

Harris, Eva ^{[7
]}

Polack, Fernando P. ^{[1
,3
]}

机构：

[1] Fdn INFANT, Gavilan 94, RA-1406 Buenos Aires, DF, Argentina

[2] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina

[3] Vanderbilt Univ, Dept Pediat, Vaccine Ctr, Nashville, TN USA

[4] Consejo Nacl Invest Cient & Tecn, Inst Ciencia & Tecnol Dr Cesar Milstein, Ctr Virol Anim CEVAN, Buenos Aires, DF, Argentina

[5] Inst Pasteur, Dept Virol, Unite Virol Struct, Paris, France

[6] Univ Buenos Aires, Fac Ciencias Exactas & Nat, CONICET UBA, Lab Virol,Dept Quim Biol IQUIBICEN, Buenos Aires, DF, Argentina

[7] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA

来源：

EBIOMEDICINE | 2017年 / 20卷

关键词：

Dengue virus; Immunocompetent mouse model; Secondary infection; Immune response; CD8(+) T lymphocytes; ORIGINAL ANTIGENIC SIN; ANTIBODY-DEPENDENT ENHANCEMENT; HEMORRHAGIC-FEVER; CELL RESPONSES; SHOCK SYNDROME; VACCINE CANDIDATES; DISEASE SEVERITY; PROTECTIVE ROLE; MICE; VIREMIA;

D O I：

10.1016/j.ebiom.2017.04.033

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouseadapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentiallywith DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed lowplatelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8(+) T lymphocyteswere found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8(+) T lymphocytes before DENV-2 challenge. Disease signswere associatedwith production of tumor necrosis factor (TNF)-a and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8(+) T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8(+) T lymphocytes in manifestations of severe dengue disease.(C) 2017 The Authors. Published by Elsevier B. V.

引用

页码：202 / 216

页数：15