The inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, are histologically characterized by an accumulation of lymphocytes and plasma cells in the lamina propria and foci of polymorphonuclear lymphocytes. An immune mechanism has long been suspected in the pathogenesis of IBD but, the etiology remains unknown. It is also not clear whether alterations in lymphocyte populations or their function mediate the mucosal injury or are epiphenomena of inflammation. Current research efforts investigating the functional properties of intestinal mucosal lymphocyte subpopulations, especially the intraepithelial lymphocytes (IEL), have been hampered by the inability to specifically identify IEL in cell suspension after isolation from intestinal specimens. The major goal of this project is to define possible phenotypic and functional differences in the mucosal lymphocyte subpopulations in IBD and normal intestine. This will be accomplished by using recently developed monoclonal antibodies that are primarily restricted to mucosal lymphocytes and IEL in particular. Monoclonal antibodies that recognize the T cell receptor gamma/delta will also be used to determine the intestinal distribution of these cells in IBD and their functional characteristics. A difference in the distribution or function of lymphocyte subpopulations in the lamina propria or epithelial compartments, may play a role in the pathogenesis of IBD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002010-03
Application #
3080934
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1991-02-15
Project End
1996-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Lai, J C; Pichardo, E M; Emond, J C et al. (2009) Resource utilization of living donor versus deceased donor liver transplantation is similar at an experienced transplant center. Am J Transplant 9:586-91
Brown Jr, Robert S (2008) Live donors in liver transplantation. Gastroenterology 134:1802-13
Verna, Elizabeth C; Hunt, Kristel H; Renz, John F et al. (2005) Predictors of candidate maturation among potential living donors. Am J Transplant 5:2549-54
Moss, J; Lapointe-Rudow, D; Renz, J F et al. (2005) Select utilization of obese donors in living donor liver transplantation: implications for the donor pool. Am J Transplant 5:2974-81
Russell, G J; Parker, C M; Sood, A et al. (1996) p126 (CDw101), a costimulatory molecule preferentially expressed on mucosal T lymphocytes. J Immunol 157:3366-74
Russell, G J; Parker, C M; Cepek, K L et al. (1994) Distinct structural and functional epitopes of the alpha E beta 7 integrin. Eur J Immunol 24:2832-41
Russell, G J; Parker, C M; Cepek, K L et al. (1994) Evidence for a structural difference in the CD7 polypeptide on human thymocytes and intraepithelial lymphocytes defined by a new monoclonal antibody, 3D9. Cell Immunol 154:153-65