Thomas J. Braciale

Education

  • BS, St. Joseph's College, Philadelphia, PA
  • MD, Univ. of Pennsylvania, Philadelphia, PA
  • PhD, Univ. of Pennsylvania, Philadelphia, PA
  • Residency, Barnes Hospital (Washington Univ.) St. Louis, MO
  • Postdoc, Australian National University, Canberra, Australia

Primary Appointment

  • Professor, Pathology

Contact

Research Interest(s)

T Lymphocyte Responses To Virus Infection

Research Description

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.

Selected Publications

  • Kim T, Gorski S, Hahn S, Murphy K, Braciale T. Distinct Dendritic Cell Subsets Dictate the Fate Decision between Effector and Memory CD8(+) T Cell Differentiation by a CD24-Dependent Mechanism. Immunity. 2014;40(3): 400-13. PMID: 24631155
  • Gorski S, Hahn Y, Braciale T. Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection. PLoS pathogens. 2013;9(9): e1003615. PMID: 24068930
  • Braciale T, Sun J, Kim T. Regulating the adaptive immune response to respiratory virus infection. Nature reviews. Immunology. 2012;12(4): 295-305. PMID: 22402670 | PMCID: PMC3364025
  • Gorski S, Hufford M, Braciale T. Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract. Current opinion in virology. 2012;2(3): 233-41. PMID: 22608464 | PMCID: PMC3378727
  • Hufford M, Richardson G, Zhou H, Manicassamy B, García-Sastre A, Enelow R, Braciale T. Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8(+) T Cells. PloS one. 2012;7(10): e46581. PMID: 23056353 | PMCID: PMC3466305
  • Kennedy J, Turner R, Braciale T, Heymann P, Borish L. Pathogenesis of rhinovirus infection. Current opinion in virology. 2012;2(3): 287-93. PMID: 22542099 | PMCID: PMC3378761
  • Yoo J, Fish E, Braciale T. LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells during respiratory virus infection. The Journal of experimental medicine. 2012;209(10): 1853-67. PMID: 22987801 | PMCID: PMC3457726
  • Braciale T, Kim T. Slowing down with age: lung DCs do it too. The Journal of clinical investigation. 2011;121(12): 4636-9. PMID: 22105176 | PMCID: PMC3226069
  • Kim T, Sun J, Braciale T. T cell responses during influenza infection: getting and keeping control. Trends in immunology. 2011;32(5): 225-31. PMID: 21435950 | PMCID: PMC3090469
  • Sun J, Cardani A, Sharma A, Laubach V, Jack R, Müller W, Braciale T. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus. PLoS pathogens. 2011;7(8): e1002173. PMID: 21829368 | PMCID: PMC3150291
  • Sun J, Dodd H, Moser E, Sharma R, Braciale T. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nature immunology. 2011;12(4): 327-34. PMID: 21297642 | PMCID: PMC3079402
  • Hufford M, Kim T, Sun J, Braciale T. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. The Journal of experimental medicine. 2010;208(1): 167-80. PMID: 21187318 | PMCID: PMC3023137
  • Kim T, Hufford M, Sun J, Fu Y, Braciale T. Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection. The Journal of experimental medicine. 2010;207(6): 1161-72. PMID: 20513748 | PMCID: PMC2882836
  • Ream R, Sun J, Braciale T. Stimulation of naive CD8+ T cells by a variant viral epitope induces activation and enhanced apoptosis. Journal of immunology (Baltimore, Md. : 1950). 2010;184(5): 2401-9. PMID: 20139280 | PMCID: PMC2996134
  • Kim T, Braciale T. Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PloS one. 2009;4(1): e4204. PMID: 19145246 | PMCID: PMC2615220
  • Stevens W, Sun J, Castillo J, Braciale T. Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-enhanced disease. Viral immunology. 2009;22(4): 243-51. PMID: 19594395 | PMCID: PMC2885249
  • Sun J, Madan R, Karp C, Braciale T. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nature medicine. 2009;15(3): 277-84. PMID: 19234462 | PMCID: PMC2693210
  • Hao X, Kim T, Braciale T. Differential response of respiratory dendritic cell subsets to influenza virus infection. Journal of virology. 2008;82(10): 4908-19. PMID: 18353940 | PMCID: PMC2346724
  • Wissinger E, Stevens W, Varga S, Braciale T. Proliferative expansion and acquisition of effector activity by memory CD4+ T cells in the lungs following pulmonary virus infection. Journal of immunology (Baltimore, Md. : 1950). 2008;180(5): 2957-66. PMID: 18292518 | PMCID: PMC2855534
  • Stevens W, Kim T, Pujanauski L, Hao X, Braciale T. Detection and quantitation of eosinophils in the murine respiratory tract by flow cytometry. Journal of immunological methods. 2007;327(1): 63-74. PMID: 17716680 | PMCID: PMC2670191
  • Yoon H, Legge K, Sung S, Braciale T. Sequential activation of CD8+ T cells in the draining lymph nodes in response to pulmonary virus infection. Journal of immunology (Baltimore, Md. : 1950). 2007;179(1): 391-9. PMID: 17579060