3rd Annual BMRP Investigator Meeting - Abstract

Deficiency of NK and CD1d-Restricted Vα24+ NK T-Cells in Crohn’s Disease and Ulcerative Colitis

Randall H. Grose, Fiona M. Thompson and Adrian G. Cummins^a

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 Vα24+ Vβ11+ T-cells.  These immunoregulatory T-cells are predominantly CD161+ NK cells and are CD1d restricted. Vα24+ T-cells are deficient in autoimmune disorders.  The aim of this study was to investigate whether regulatory Vα24+ 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 Vα24+, Vβ11+, Vβ13+ T-cells were determined.  Intracellular IL-4 and IFN-γ production was measured after in vitro anti-CD3 antibody stimulation.  Relative duplex PCR from ileal or colonic biopsy samples was used to determine Vα24 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.  Vα24+, Vα24+ CD4+, Vα24+ Vβ11+ T-cells and CD161+ Vα24+ NK T-cells were reduced to 34%, 45%, 21% and 25% of levels in normal controls, respectively, in Crohn’s disease.  The Vα24+ Vβ11+ and Vα24+ Vβ11+ α-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-γ production by Vα24+ T-cells were defective.  Intestinal Vα24 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. Vα24+ T-cells are deficient and functionally defective in Crohn’s disease and are selectively and mucosally deficient in ulcerative colitis.  Vα24+ Vβ11+ and Vα24+ Vβ11+ α-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