Thomas J. Braciale, Md, PhD
Graduate School: University of Pennsylvania
Primary Appointment: Professor, Pathology
T Lymphocyte Responses To Virus Infection
Email Address: email@example.com
My laboratory is interested in the host immune response to virus infection - specifically, we study the role of the adaptive immune response in the clearance of both virus and virus-infected cells from the body, and the contribution of the immune response in producing injury during virus infection. Much of our work focuses on infection of the respiratory tract (the lungs) by two viruses: Influenza virus and Respiratory Syncytial Virus (RSV).
Our research on Influenza focuses on the response of CD8+ T lymphocytes -- Cytolytic T Lymphocytes (CTL) or killer T cells -- to Influenza infection. We want to understand three main things: 1) how CTL are generated during infection; 2) how CD8+ T cells interact with the principal antigen presenting cells of the body (i.e. dendritic cells) to produce those CTL; and 3) how the interplay between Influenza virus and the CTL response contributes to lung injury during infection. We use modern techniques of cell and molecular biology -- including T cell receptor transgenic murine models and virus reverse genetics (to alter the structure of the Influenza genome) in order to understand how specific virus genes (and their products), as well as CTL products (e.g. cytokines) operate to clear infection and/or produce disease. Recently, we have extended this work to include avian influenza virus ("Bird Flu") infection in order to define the mechanisms of lethal infection produced by this virus.
The second virus that we study, RSV, is a major cause of severe lung infection in young infants; and there is currently no safe vaccine for this virus. Immunization with conventional RSV vaccines (e.g. killed virus) results in more severe injury after subsequent natural RSV infection (when compared to natural infection alone). Thus, RSV can induce immune-mediated disease, and can inhibit the normal immune response. Our research in this area is aimed at understanding how this virus can dysregulate the immune response; so safe and effective vaccines can be developed.
In addition to our work in Influenza and RSV, our laboratory has also become involved in Bio-Defense research. Our current project is aimed at the development of new vaccines against the small pox virus when delivered as a weapon of bio-terrorism. We are employing a murine model of small pox infection using the murine equivalent of the virus (i.e. ectromelia or mouse pox virus). We are using innovative methods to clone and express genes from vaccinia virus (the pox virus used to vaccinate humans against small pox) to identify candidate proteins which could serve as the basis for vaccines directed against small pox infection.
Yoo JK, Fish EN, Braciale TJ. LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells during respiratory virus infection. J Exp Med. 2012 Sep 24;209(10):1853-67. Epub 2012 Sep 17.
Gorski SA, Hufford MM, Braciale TJ. Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract. Curr Opin Virol. 2012 Jun;2(3):233-41. doi: 10.1016/j.coviro.2012.04.006. Epub 2012 May 17. Review.
Braciale TJ, Sun J, Kim TS. Regulating the adaptive immune response to respiratory virus infection. Nat Rev Immunol. 2012 Mar 9;12(4):295-305. doi: 10.1038/nri3166. Review.
Hufford MM, Richardson G, Zhou H, Manicassamy B, García-Sastre A, Enelow RI, Braciale TJ. Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8(+) T Cells. PLoS One. 2012;7(10):e46581. doi: 10.1371/journal.pone.0046581. Epub 2012 Oct 8.
Braciale TJ, Kim TS. Slowing down with age: lung DCs do it too. J Clin Invest. 2011 Dec;121(12):4636-9. doi: 10.1172/JCI61367. Epub 2011 Nov 21.
Sun J, Cardani A, Sharma AK, Laubach VE, Jack RS, Müller W, Braciale TJ. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus. PLoS Pathog. 2011 Aug;7(8):e1002173. doi: 10.1371/journal.ppat.1002173. Epub 2011 Aug 4.
Kim TS, Sun J, Braciale TJ. T cell responses during influenza infection: getting and keeping control. Trends Immunol. 2011 May;32(5):225-31. doi: 10.1016/j.it.2011.02.006. Epub 2011 Mar 23. Review.
Sun J, Dodd H, Moser EK, Sharma R, Braciale TJ. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol. 2011 Apr;12(4):327-34. doi: 10.1038/ni.1996. Epub 2011 Feb 6.
Hufford MM, Kim TS, Sun J, Braciale TJ. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J Exp Med. 2011 Jan 17;208(1):167-80. doi: 10.1084/jem.20101850. Epub 2010 Dec 27.
|Office Address:||PO Box 801386 MR-6, 3709A, MR-6 3525,|