3rd Annual BMRP Investigator Meeting - Abstract

Deficiency of NK and CD1d-Restricted Va24+ NK T-Cells in Crohn’s Disease and Ulcerative Colitis

Randall H. Grose, Fiona M. Thompson and Adrian G. Cumminsa

Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital (Woodville South, South Australia, Australia)

Background: A subset of immunoregulatory T-cells has the surface phenotype of Va24+ Vb11+ T-cells.  These immunoregulatory T-cells are predominantly CD161+ NK cells and are CD1d restricted. Va24+ T-cells are deficient in autoimmune disorders.  The aim of this study was to investigate whether regulatory Va24+ T-cells are deficient in Crohn’s disease or ulcerative colitis.

Method: Blood was collected for flow cytometry from subjects with Crohn’s disease (n=97), ulcerative colitis (n=68) and control subjects (n=152).  Numbers of circulating CD56+, CD57+, CD94+, CD161+ NK cells and Va24+, Vb11+, Vb13+ T-cells were determined.  Intracellular IL-4 and IFN-g production was measured after in vitro anti-CD3 antibody stimulation.  Relative duplex PCR from ileal or colonic biopsy samples was used to determine Va24 mRNA expression.
 
Results: CD56+, CD57+, CD94+, CD161+ NK cells were reduced to 38%, 70%, 55% and 47% in Crohn’s disease of levels in normal controls.  Similarly, CD56+, CD57+, CD94+, CD161+ NK cells were reduced to 56%, 73%, 59% and 67% in ulcerative colitis subjects.  Va24+, Va24+ CD4+, Va24+ Vb11+ T-cells and CD161+ Va24+ NK T-cells were reduced to 34%, 45%, 21% and 25% of levels in normal controls, respectively, in Crohn’s disease.  The Va24+ Vb11+ and Va24+ Vb11+ a-galactosylceramide/CD1d+ T-cells were 21% and 0.3% in Crohn’s disease and 15% and 7% in ulcerative colitis compared to normal subjects.  IL-4 and IFN-g production by Va24+ T-cells were defective.  Intestinal Va24 mRNA expression from Crohn’s disease and ulcerative colitis was 15% and 29%, respectively, of levels in normal subjects.

Conclusion: We conclude that NK cells are deficient in Crohn’s disease and in ulcerative colitis. Va24+ T-cells are deficient and functionally defective in Crohn’s disease and are selectively and mucosally deficient in ulcerative colitis.  Va24+ Vb11+ and Va24+ Vb11+ a-galactosylceramide/CD1d tetramer+ cells are deficient in both Crohn’s disease and ulcerative colitis.  This decrease in immunoregulatory cells may contribute to the pathogenesis of IBD.

^aPrincipal Investigator