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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3671-3678. Prepublished online as a Blood First Edition Paper on August 19, 2008; DOI 10.1182/blood-2008-05-157016. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-05-157016v1 112/9/3671    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yu, C. I. Articles by Palucka, A. K. Search for Related Content PubMed PubMed Citation Articles by Yu, C. I. Articles by Palucka, A. K. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with influenza virus vaccines Chun I. Yu1,2, Michael Gallegos1, Florentina Marches1, Gerard Zurawski1, Octavio Ramilo1,3, Adolfo García-Sastre4, Jacques Banchereau1, and A. Karolina Palucka1 1 Baylor National Institute of Allergy and Infectious Diseases (NIAID) Cooperative Center for Translational Research on Human Immunology, INSERM U899, Baylor Institute for Immunology Research, Dallas, TX; 2 Baylor University, Waco, TX; 3 University of Texas Southwestern, Dallas, TX; and 4 Department of Microbiology, Emerging Pathogens Institute, and NIAID Center for Investigating Virus Immunity and Antagonism, Mount Sinai School of Medicine, New York, NY The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) β2 microglobulin–/– mice, engrafted with human CD34+ hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus vaccine induces expansion of CD8+ T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8+ T cells produce IFN- and express cell-surface CD107a. FluM1-specific CD8+ T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus vaccine. Expansion of antigen-specific CD8+ T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity, including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn, will allow a new approach to the rational design and preclinical testing of vaccines that cannot be tested in human volunteers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kwant-Mitchell, A. A. Ashkar, and K. L. Rosenthal Mucosal Innate and Adaptive Immune Responses against Herpes Simplex Virus Type 2 in a Humanized Mouse Model J. Virol., October 15, 2009; 83(20): 10664 - 10676. [Abstract] [Full Text] [PDF] J. Unsinger, J. S. McDonough, L. D. Shultz, T. A. Ferguson, and R. S. Hotchkiss Sepsis-induced human lymphocyte apoptosis and cytokine production in "humanized" mice J. Leukoc. Biol., August 1, 2009; 86(2): 219 - 227. [Abstract] [Full Text] [PDF]

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