O'Keeffe, Joan and Doherty, Derek G. and Kenna, Tony and Sheahan, Kieran and O'Donoghue, Diarmuid P. and Hyland, John M. and O'Farrelly, Cliona
Diverse populations of T cells with NK cell
receptors accumulate in the human intestine in
health and in colorectal cancer.
European Journal of Immunology, 34.
T cells expressing NK cell receptors (NKR) display rapid MHC-unrestricted cytotoxicity and
potent cytokine secretion and are thought to play roles in immunity against tumors. We have
quantified and characterized NKR+ T cells freshly isolated from epithelial and lamina propria
layers of duodenum and colon from 16 individuals with no evidence of gastrointestinal disease
and from tumor and uninvolved tissue from 19 patients with colorectal cancer. NKR+ T
cell subpopulations were differentially distributed in different intestinal compartments, and
CD161+ T cells accounted for over one half of T cells at all locations tested. Most intestinal
CD161+ T cells expressed Â§ g TCR and either CD4 or CD8. Significant proportions expressed
HLA-DR, CD69 and Fas ligand. Upon stimulation in vitro, CD161+ T cells produced IFN- + and
TNF- Â§ but not IL-4. NKT cells expressing the V Â§ 24V g 11 TCR, which recognizes CD1d, were virtually absent from the intestine, but colonic cells produced IFN- + in response to the NKT cell agonist ligand Â§ -galactosylceramide. NKR+ T cells were not expanded in colonic tumors compared to adjacent uninvolved tissue. The predominance, heterogeneity and differential distribution of NKR+ T cells at different intestinal locations suggests that they are central to ntestinal immunity.
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