Thomas J. Braciale
Primary AppointmentProfessor, Pathology
- BS, Biology, St. Joseph's College, Philadelphia, PA
- MD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
- PhD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
- Residency, Pathology, Barnes Hospital (Washington Univ.) St. Louis, MO
- Postdoc, Immunology and Virology, Australian National University, Canberra, Australia
T Lymphocyte Responses To Virus Infection
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.