Continuous CD27 triggering in vivo strongly reduces NK cell numbers.
NK cells are important mediators of the early defense. In mice, immature and mature NK (mNK) cells constitutively express the TNF receptor family member CD27; however, mNK cells eventually lose CD27 expression and become resting NK cells. Interaction of CD27 with its ligand, CD70, enhances proliferation and effector functions of NK cells. We used mice that constitutively express CD70 on B cells (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27 expression on NK cells and gradually reduced absolute NK cell numbers. This reduction was most prominent in the mNK cell subpopulation and was at least partially due to increased apoptosis. Residual NK cells showed lower expression of activating Ly49 receptors and normal (liver) or decreased (spleen) IFN-gamma production. Nevertheless, NK cells from CD70-Tg mice displayed higher YAC-1 killing capacities. CD70-Tg NK cells exhibited up-regulated expression of NKG2D, which is in accordance with the increased YAC-1 lysis, as this is mainly NKG2D-dependent. Taken together, this study is the first to demonstrate that continuous CD70 triggering of CD27 on NK cells in vivo results in a severe reduction of NK cells. On a single cell basis, however, residual NK cells display enhanced cytotoxicity.
Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
Veerle
V
De Colvenaer
Sylvie
S
Taveirne
Jörg
J
Hamann
Alex M
AM
de Bruin
Magda
M
De Smedt
Tom
T
Taghon
Bart
B
Vandekerckhove
Jean
J
Plum
René
R
van Lier
Georges
G
Leclercq
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D053282:CD27 Ligand / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D000950:Antigens, Ly; D053282:CD27 Ligand; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7