T Cell Tolerance
My lab has focused on understanding the mechanisms that determine whether T cells are activated or tolerized in vivo. We use a variety of transgenic and gene knock out mouse models to evaluate the molecular pathways that govern T cell fate. In particular, we examine how to promote T cell responses to tissues, with a goal to understand and control autoimmune and anti-tumor immune responses.
Our recent studies have examined novel ways that dendritic cells are programmed to influence T cell function in vivo. In addition we are focused on how the tissue or tumor microenvironment can have a significant impact on T cell responses.
Importantly, my interests have also expanded to establishing an immune therapy platform. My group has developed the ability to grow tumor infiltrating T cells and characterize their properties. We have also coordinated clinical trials and are building towards a comprehensive program in immune therapy.
My lab pursues three basic directions.
1) Investigating the role of survival versus apoptosis on tolerance and autoimmunity.
2) Investigating signaling pathways that control T cell tolerance, activation, immunity, autoimmunity or tumor immunity.
3) Examining the potential for immune surveillance and tumor immune therapy.
Graduate Students:
Post- Doctoral Fellows
- Sara Hamilton
- Evan Lind
- Kiichi Murakami
- Ramtin Rahbar
Selected References:
Link to Pubmed Publications-
Calzascia, T., Pellegrini, M., Hall, H., Sabbagh, L., Ono, N., Elford, A.R., Ohashi, P.S. (2007) TNF-alpha is critical for antitumor but not anti-viral T cell immunity. J. Clin. Invest. (in press).
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Gronski, M.A., Boulter, J.M., Moskophidis, D., Nguyen, L.T., Holmberg, K., Elford, A.R., Deenick, E.K., Kim, H.O., Penninger, J.M., Odermatt, B., Gallimore, A., Gascoigne, N.R.J. and Ohashi, P.S. (2004) TCR affinity and negative regulation limit autoimmunity. Nature Med. 10:1234-1239.
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Millar, D.G., Garza, K.M., Odermatt, B., Elford, A.R., Ono, N., Li, Z. and Ohashi, P.S. (2003) Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo. Nat. Med. 9:1469-1476.
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Nguyen, L.T., Elford, A.R., Murakami, K., Garza, K.M., Schoenberger, S.P., Odermatt, B., Speiser, D. and Ohashi, P.S. (2002) Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance. J Exp Med 195:423-35.
