Lymphocyte homing directs lymphocyte subsets to specialized microenvironments and targets immune effector cells in a tissue specific fashion, focussing regional immune responses. The molecules mediating the multi-step paradigm for lymphocyte homing have been described in detail for peripheral tissues such as the skin and gut (Butcher EC, et al. Adv in Immunol 1999;72:209-253). However, in the liver, the molecules involved have not been well defined. Hepatitis, including viral and non-viral etiologies, is an increasing cause of morbidity and mortality in the United States. My hope is to help define novel molecular targets to control hepatic inflammatory responses. My long term objectives are to do bench research at a university setting, where I can pursue my interest in immune-related diseases such as viral hepatitis and autoimmune hepatitis in a didactic atmosphere nurtured by patient care and teaching. To foster that interest, my research will be done in a lab that specializes in understanding the molecular basis of complex, in vivo immunological phenomena in peripheral tissues such as skin, gut or liver. To that end, an animal model has been created by adoptively transferring ovalbumin (OVA) -specific T-cell receptor (TCR) transgenic T cells from DO. 11.10 mice into syngeneic, Balb/c mice to amplify an antigen specific immune response. Subsequently, the livers of recipient mice are transduced with an adenovirus encoding recombinant OVA to supply a cognate liver-specific antigen. By generating a liver-selective immune response with TCR transgemc CD4 cells, which can be easily identified with the KJ1-26 (anti-transgenic TCR) mAb through flow cytometry, I will be able to define unique features or combinations of molecules (including homing, adhesion or chemokine receptors) that may define hepatic memory and effector cells, and distinguish them from well-defined cutaneous and intestinal memory and effector cells. Such molecules may define unique functional homing (or other) properties of hepatic memory T cells, and may allow identification and monitoring of these cells among circulating memory cells in man. The proposed studies have the potential to lead to novel therapeutic targets for the control of hepatic inflammatory response.
| Sato, Tohru; Habtezion, Aida; Beilhack, Andreas et al. (2006) Short-term homing assay reveals a critical role for lymphocyte function-associated antigen-1 in the hepatic recruitment of lymphocytes in graft-versus-host disease. J Hepatol 44:1132-40 |
| Staton, Tracy L; Habtezion, Aida; Winslow, Monte M et al. (2006) CD8+ recent thymic emigrants home to and efficiently repopulate the small intestine epithelium. Nat Immunol 7:482-8 |
