Lay Summary

Proposal No.  IBD-0029
Principal Investigator:  Adrian Cummins, M.D., Ph.D.
Applicant Organization:  The Queen Elizabeth Hospital (Woodville South, Australia)
Project Title:  Deficiency of immunoregulatory NK T cells in inflammatory bowel disease
Award Period: November 1, 2002 - March 31, 2005

Inflammatory bowel disease (IBD) causes inflammation of the small or large intestines that is often recurrent.  It is thought to be due to inappropriate overactivity of the immune system in the intestines.  Normally, such overactivity is suppressed by mechanisms that are still unclear.  If this system fails, IBD results.

This proposal investigates whether patients with IBD have a deficiency of a special immune suppressor cell called the ‘NK T cell.’  NK T cells are present in both the blood and in the intestinal tissue.  We will count the number of these cells in blood and measure the Vα24+ gene of these NK T cells in the intestines.  Our initial studies have shown that these cells are markedly reduced in the blood of subjects with IBD.  We need to determine whether NK T cells are also deficient in the intestines.  We will also measure whether NK T cells can produce the normal chemicals (cytokines) that directly suppress other immune cells from being activated.  NK T cells also destroy special dendritic cells that bind antigens from bacteria to activate lymphocytes.  We will therefore examine whether NK T cells are capable of killing these dendritic cells in IBD using assays in blood.  Depending on the results of the study, it may be possible to propose treatments to either stimulate NK T cells to work normally in IBD patients or to design local gene therapy of the intestines to replenish the deficiency of NK T cells.