Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597521
5. Virus Immunology
Georg Thieme Verlag KG Stuttgart · New York

Lack of NKp80 expression define a liver-resident CD49a(+) NK cell subset with ILC1-like features

B Krämer
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
P Lutz
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
C Finnemann
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
A Glässner
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
F Goeser
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
D Kaczmarek
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
J Pollok
2   University of Bonn, Department of Surgery, University of Bonn, Bonn, Germany, Bonn, Germany
,
J Bierwolf
2   University of Bonn, Department of Surgery, University of Bonn, Bonn, Germany, Bonn, Germany
,
J Trebicka
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
CP Strassburg
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
U Spengler
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
,
J Nattermann
1   University of Bonn, Department of Internal Medicine I, University of Bonn, Bonn, Germany, Bonn, Germany
› Author Affiliations
Further Information
Krämer, Benjamin

Publication History

Publication Date:
19 December 2016 (online)

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    Background: The human liver contains a unique CD49a+ NK cell subset that resembles murine liver-resident NK cells. At the moment it is not fully understood if these cells have conventional NK cell or ILC-(innate lymphoid cells) type 1-like features. For this reason we have analyzed liver CD49a(+) NK cells in more detail and compare them with similar CD49a(+) cells from the gastrointestinal (GI) tissues.

    Material and Methods: Human tissue-infiltrating lymphocytes were isolated from 15 liver-perfusates, 12 -resections, 18 -explants, 29 -biopisies and 33 biopsies from normal gastrointestinal tissues. Lymphocytes were phenotypically characterized by multicolor flowcytometry and tested for cytokine production following PMA/ionomycin stimulation.

    Results: Analyzing liver infiltrating CD49a(+) CD94(+) CD56(+)CD3(-)NK cells, we found 2 distinct subsets defined by expression of the NK cell activating receptor NKp80. Unlike CD49a(+)Nkp80(+) cells, the CD49a(+)NKp80(-) subset is negative for the transcription factor EOMES and express the cytolytic effector molecule perforin at low levels. Markers for tissue resident lymphocytes like CD69 [NKp80(-): 38% vs. NKp80(+): 35%] and CD103 [NKp80(-): 39% vs. NKp80(+): 31%] are expressed on both CD49a(+) subsets. The capacity to produce IFNγ do not vary between these cells. Surprisingly, frequency of CD49a(+)Nkp80(-) cells is very low in liver tissue (0.3% lymphocytes) and is not significantly different to CD49a(+)Nkp80(+)(0.63%) or to liver ILC1/ILC2/ILC3 (0.64%).

    CD49a(+)NKp80(-) CD94(+) NK cells could also be detected in gastrointestinal tract: stomach (0.8% of lymphocytes) and duodenum (0.5%) have significantly higher frequencies of this subset, whereby frequencies in esophagus (0.2%), ileum (0.3%) and colon (0.3%) are comparable to liver tissues. CD49a(+)NKp80(-) CD94(+) NK cells from GI tract are abundant for expression of CD103, CD69 and NKp44. Recently, these cells were described as CD103(+) intraepithelial ILC1.

    Conclusion: Liver CD49a(+)NKp80(-) NK cells share some features of non-conventional NK cells and are maybe a counterpart of mucosal CD103(+) intraepithelial ILC1.


     

    No conflict of interest has been declared by the author(s).

    Krämer, Benjamin