MICaB Graduate Program
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Brian T. Fife, Ph.D.
Department of Medicine
Northwestern University, 2001, Ph.D.
Office phone: 612-624-2417
Lab phone: 612-624-6149
Autoimmunity, tumor immunology, immunological tolerance, intravital 2 photon 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. In the case of chronic viral infections or tumor immunology these pathways can be selectively targeted to restore T cell function and invigorate an exhausted T cell response. 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, tumor immunology, autoimmune diseases, and transplantation.
- Pauken KE, Linehan JL, Spanier JA, Sahli NL, Kalekar LA, Binstadt BA, Moon JJ, Mueller DL, Jenkins MK, and Fife BT. 2013. Cutting Edge: Type 1 Diabetes Occurs Despite Robust Anergy Among Endogenous Insulin-Specific CD4 T Cells in NOD Mice. J Immunol. Oct 11. (in press)
- Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, Munn DH, Murphy WJ, Azuma M, Yagita H, Fife BT, Sayegh MH, Najafian N, Socie G, Ahmed R, Freeman GJ, Sharpe AH, Blazar BR. 2013. Host programmed death ligand-1 is dominant over programmed death ligand-2 expression in regulating graft-versus-host disease lethality. Blood. Sep 12. (in press)
- Mitchell JS, Burbach BJ, Srivastava R, Fife BT, Shimizu Y. 2013. Multistage T cell-dendritic cell interactions control optimal CD4 T cell activation through the ADAP-SKAP55-signaling module. J Immunol. Sep 1;191(5):2372-83.
- Gerner MY, Heltemes-Harris LM, Fife BT, Mescher MF. 2013. Cutting edge: IL-12 and type I IFN differentially program CD8 T cells for programmed death 1 re-expression levels and tumor control. J Immunol. Aug 1;191(3):1011-5.
- Pauken KE, Jenkins MK, Azuma M, and Fife BT. 2013. PD-1, but not PD-L1, expressed by islet-reactive CD4+ T cells suppresses infiltration of the pancreas during type 1 diabetes. Diabetes. Aug;62(8):2859-69.
- Melton AC, Bailey-Bucktrout SL, Travis MA, Fife BT, Bluestone JA, Sheppard D. 2010. Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J Clin Invest. Dec;120(12):4436-44.
- Catron DM, Pape KA, Fife BT, van Rooijen N, Jenkins MK. 2010. A protease-dependent mechanism for initiating T-dependent B cell responses to large particulate antigens. J Immunol. Apr 1;184(7):3609-17.
- Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, and Bluestone JA. 2009. Interactions between programmed death-1 and programmed death ligand-1 promote tolerance by blocking the T cell receptor-induced stop signal. Nat Immunol. Nov;10(11):1185-92.
- 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.
- 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.
- 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.
- 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.
Publications at Pubmed