Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus

被引:103
作者
Roti, Michelle [2 ]
Yang, Junbao [2 ]
Berger, DeAnna [2 ]
Huston, Laurie [2 ]
James, Eddie A. [2 ]
Kwok, William W. [1 ,2 ]
机构
[1] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[2] Benaroya Res Inst Virginia Mason, Seattle, WA USA
关键词
D O I
10.4049/jimmunol.180.3.1758
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It is commonly perceived that the human immune system is naive to the newly emerged HSN1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4+ T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4+ T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4+ T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
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收藏
页码:1758 / 1768
页数:11
相关论文
共 33 条
[1]   SEQUENCE RELATIONSHIPS AMONG THE HEMAGGLUTININ GENES OF 12 SUBTYPES OF INFLUENZA-A VIRUS [J].
AIR, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (12) :7639-7643
[2]  
[Anonymous], 1980, B WORLD HEALTH ORGAN, V58, P585
[3]  
[Anonymous], 2006, Wkly Epidemiol Rec, V81, P249
[4]  
[Anonymous], 2007, WEEKLY EPIDEMIOLOGIC
[5]   Current concepts - Avian influenza A (H5N1) infection in humans [J].
Beigel, H ;
Farrar, H ;
Han, AM ;
Hayden, FG ;
Hyer, R ;
de Jong, MD ;
Lochindarat, S ;
Tien, NTK ;
Hien, NT ;
Hien, TT ;
Nicoll, A ;
Touch, S ;
Yuen, KY .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (13) :1374-1385
[6]   Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes [J].
Boon, ACM ;
de Mutsert, G ;
van Baarle, D ;
Smith, DJ ;
Lapedes, AS ;
Fouchier, RAM ;
Sintnicolaas, K ;
Osterhaus, ADME ;
Rimmelzwaan, GF .
JOURNAL OF IMMUNOLOGY, 2004, 172 (04) :2453-2460
[7]   CD4 T cell-mediated protection from lethal influenza: Perforin and antibody-mediated mechanisms a one-two punch [J].
Brown, Deborah M. ;
Dilzer, Allison M. ;
Meents, Dana L. ;
Swain, Susan L. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (05) :2888-2898
[8]   Ab and T cell epitopes of influenza A virus, knowledge and opportunities [J].
Bui, Huynh-Hoa ;
Peters, Bjoern ;
Assarsson, Erika ;
Mbawuike, Innocent ;
Sette, Alessandro .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (01) :246-251
[9]   HLA class II-restricted CD4+ T cell responses directed against influenza viral antigens postinfluenza vaccination [J].
Danke, NA ;
Kwok, WW .
JOURNAL OF IMMUNOLOGY, 2003, 171 (06) :3163-3169
[10]   Avian influenza A (H5N1) [J].
de Jong, MD ;
Hien, TT .
JOURNAL OF CLINICAL VIROLOGY, 2006, 35 (01) :2-13