Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis.
While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-gamma, whereas comparable cells from CD patients produce large amounts of IFN-gamma and small amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/anti-CD28 or with B cells expressing transfected CD1d induces substantial IL-13 production. While this provided firm evidence that the IL-13-producing cell is an NK T (NKT) cell, it became clear that this cell does not express invariant NKT cell receptors characteristic of most NKT cells since there was no increase in cells binding alpha-galactosylceramide-loaded tetramers, and alpha-galactosylceramide did not induce IL-13 secretion. Finally, we show that both human NKT cell lines as well as UC CD161(+) LPT cells are cytotoxic for HT-29 epithelial cells and that this cytotoxicity is augmented by IL-13. These studies show that UC is associated with an atypical Th2 response mediated by nonclassical NKT cells producing IL-13 and having cytotoxic potential for epithelial cells.
Fuss
Ivan J
IJ
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda Maryland 20892, USA. ifuss@niaid.nih.gov
Heller
Frank
F
Boirivant
Monica
M
Leon
Francisco
F
Yoshida
Masaru
M
Fichtner-Feigl
Stefan
S
Yang
Zhiqiong
Z
Exley
Mark
M
Kitani
Atsushi
A
Blumberg
Richard S
RS
Mannon
Peter
P
Strober
Warren
W
D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D016022:Case-Control Studies; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D018793:Interleukin-13; D007371:Interferon-gamma