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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 13, 2008 Accepted August 4, 2008 Broad influenza-specific CD8+ T cell responses in humanized mice vaccinated with influenza virus vaccines Chun I. Yu, Michael Gallegos, Florentina Marches, Gerard Zurawski, Octavio Ramilo, Adolfo Garcia-Sastre, Jacques Banchereau, and A. Karolina Palucka* Baylor University, Waco, Texas Baylor Institute for Immunology Research, Baylor Research Institute, Dallas Department of Pediatrics, UT Southwestern, Dallas Department of Microbiology, Mount Sinai School of Medicine, New York * Corresponding author; email: karolinp{at}baylorhealth.edu. 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 non-obese diabetic severe combined immunodeficiency (NOD/SCID) 2 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 (LAIV) vaccine induces expansion of CD8+ T cells specific to influenza matrix protein (FluM1) and non-structural protein 1 (NS1) in blood, spleen and lungs. Upon 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 (TIV) 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 which 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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