Brian T. Fife, Ph.D. Assistant Professor Department of Medicine Northwestern University, 2001, Ph.D. Office phone: 612-624-2417 Lab phone: 612-624-6149 bfife@umn.edu

Research Interests:

Autoimmunity, immunological tolerance, intravital imaging

The processes underlying T lymphocyte activation and effector function are critical for the regulation of autoimmune disease, prevention of transplant rejection and the development of vaccines. We have identified two key regulatory pathways; Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed Death-1 (PD-1) that are important negative regulators of T cell function. Our research is focused on understanding the biology of these pathways as well as discovering/applying novel methods to deliver signals through inhibitory molecules like CTLA-4 and/or PD-1 to control autoimmunity and prevent transplant rejection. We have shown that these pathways control both anergy induction and long term maintenance of tolerance using an autoimmune diabetes model. Recent studies have focused on the in vivo imaging of the immune response using two photon microscopy. Imaging these cells in vivo will allow us to determine the precise roles of these negative regulatory pathways at different stages during disease pathogenesis to control immunity and enhance tolerance. It is our hypothesis that these basic mechanisms controlling T cells can be applied during chronic viral infections, autoimmune diseases, and transplantation.

Publications:

• Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, and Bluestone JA. Interactions between programmed death-1 and programmed death ligand-1 promote tolerance by blocking the T cell receptor-induced stop signal. Nature Immunology (In press).
• Fife BT and Bluestone JA. 2008. Control of peripheral T cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. Aug;224(1):166-82.
• Zhou X, Jeker LT, Fife BT, Zhu S, Anderson M, McManus MT, and Bluestone JA. 2008. Selective miRNA disruption in Tregs leads to uncontrolled autoimmunity. J Exp Med. Sep 1;205(9):1983-91.
• Habicht A, Dada S, Jurewicz M, Fife BT, Yagita H, Azuma M, Sayegh MH, Guleria I. 2007. A Link between PDL1 and T Regulatory Cells in Fetomaternal Tolerance. J Immunol. Oct 15;179(8):5211-5219.
• Guleria I, Gubbels Bupp M, Dada S, Fife B, Tang Q, Ansari MJ, Trikudanathan S, Vadivel N, Fiorina P, Yagita H, Azuma M, Atkinson M, Bluestone JA, Sayegh MH. 2007. Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clin Immunol. Oct;125(1):16-25.
• Fife BT, Guleria I, Gubbels-Bupp M, Eagar TN, Tang Q, Bour-Jordan H, Yagita H, Azuma M, Sayegh MH and Bluestone JA. 2006. Insulin-induced remission in new onset NOD mice is maintained by the PD-1/PD-L1 pathway. J Exp Med. Nov 27;203(12):2737-47.
• Fife BT, Griffin MD, Abbas AK, Locksley RM, and Bluestone JA. 2006. Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist. J Clin Invest. Aug;116(8):2252-61.
• Karpus WJ, Kennedy KJ, Fife BT, Bennett JL, Dal Canto MC, Kunkel SL, Lukacs NW. 2006. Anti-CCL2 treatment inhibits Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Neurovirol. Aug;12(4):251-61.
• Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, and Bluestone JA. 2006. Visualizing regulatory T cell control of autoimmune responses in non-obese diabetic mice. Nature Immunology Jan;7(1):83-92.
• Elhofy A, Kennedy KJ, Fife BT, Karpus WJ. 2002. Regulation of experimental autoimmune encephalomyelitis by chemokines and chemokine receptors. Immunol Res. 25(2):167-75.
• Fife BT, Paniagua MC, Lukacs NW, Kunkel SL, and Karpus WJ. 2001. Selective CCR1 expression by central nervous system-infiltrating encephalitogenic T cells during experimental autoimmune encephalomyelitis. J Neurosci Res. Nov 15;66(4):705-14.
• Fife BT, Kennedy KJ, Paniagua MC, Lukacs NW, Kunkel SL, Luster AD, and Karpus WJ.2001. CXCL10 (IFN-g-inducible protein-10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol. Jun 15;166(12):7617-24.
• Fife BT, Huffnagle GB, Kuziel WA, and Karpus WJ. 2000. CC chemokine receptor 2 is critical for the induction of experimental autoimmune encephalomyelitis. J Exp Med. Sep 18;192(6):899-905.

Last updated: August 24, 2009