|Department of Immunology - University of Toronto||Faculty of Medicine / University of Toronto|
|Home | Search | Site Map | Login|
|> Immunology Home > Faculty > Faculty Directory > TANIA H. WATTS, Ph.D.|
TANIA H. WATTS, Ph.D.
1) Tania Watts currently holds the Sanofi Pasteur Chair in Human Immunology
2) Tania Watts is Director of the Toronto Human Immunology Network, a FOCiS Center of Excellence
Upon infection, the innate and then the adaptive immune system are rapidly ramped up to control and then clear the infection. When T cells are activated, in addition to developing effector functions that aid in clearing of the infection, they also upregulate members of the tumor necrosis factor receptor (TNFR) family (1). This family of receptors plays an important role in controlling life and death in the immune system. Our lab has shown that the TNFR family members 4-1BB and GITR are critical for sustaining CD8 T cell survival in the lung during acute severe respiratory influenza infection. We provided evidence that the immune system uses antigen–inducible TNFRs such as 4-1BB to control the duration of T cell response according to the persistence of the virus, thereby allowing a response that is sufficient to clear the virus, but is down regulated once the virus is cleared to protect the host from pathology (2-5). This led us to ask what happens when the virus cannot be cleared, such as occurs with HIV infection of humans or lymphocytic choriomeningitis virus clone 13 infection of mice.
In the event that a virus cannot be eliminated from the host, immune regulatory mechanisms come into play that allow a détente to be reached between the host and pathogen, thereby balancing immune control of the pathogen against collateral damage. In the last few years, studies of chronic viral infection in mice and humans have revealed several inhibitory mechanisms that are induced during chronic viral infection to prevent immune pathology. While it is clear that these inhibitory mechanisms are important, the question remained as to what happens to inducible stimulatory receptors when virus persists. Recently we showed that although 4-1BB expression persists on the LCMV specific CD8 T cells at the chronic phase of infection with the clone 13 variant of LCMV, the 4-1BB signaling pathway becomes desensitized due to loss of one of its key signaling adaptors, TRAF1 (6). TRAF1 is also lost from HIV specific T cells with progression of HIV, but maintained at higher levels in those individuals that can control their HIV infection(6). Moreover, the TRAF1 levels inversely correlate with viral load.
Another interest of our laboratory is to understand the mechanisms that control the persistence of memory T cells as well as the survival of immune related cancer cells. We have shown that the TNF family ligand 4-1BBL plays a key role in sustaining the survival of memory T cells in the weeks after the virus is cleared (7). Interestingly, incorporating 4-1BBL into an adenovirus vaccine vector can prolong the duration of CD8 T cell mediated protection to influenza virus in mice (8). The signaling adaptor TRAF1 is important for the persistence of activated and memory T cells, at least in part through its affects on decreasing the levels of the proapoptotic molecule BIM (9-11). A current interest therefore, is to understand the role of TRAF1 expression in leukemia and lymphoma.
My laboratory also has a strong interest in T cell immunity to viruses, including HIV and influenza virus, in humans. In recent studies, we have explored the state of T cell memory to influenza virus in older people and found that the memory CD8 T cells expressed markers of terminal differentiation and senescence commonly found in T cells specific for persisting pathogens such as CMV. We found that the presence of this influenza specific KLRG1hiCD57hi T cell population was a predictor of a poor antibody response to vaccination to seasonal H1N1 influenza (12). We have also examined the state of immunity to A/2009 pandemic influenza in the Toronto population at 1 year post-pandemic.
Our research is currently funded by the Canadian Institutes for Health Research and the Canadian Cancer Society.
Faculty of Medicine | University of Toronto
Home | Search | Site Map | Login
About Us | Faculty | Research | Seminars | Undergraduate | Graduate | Post-Doctoral
All contents copyright © 2004 University of Toronto. All rights reserved.