title: CD27-deficient mice show normal NK-cell differentiation but impaired function upon stimulation.
abstract: Natural killer (NK) cells are part of the first line defense against tumors, parasites and virus-infected cells. Therefore, factors that control NK-cell numbers and their function are important. CD27 is constitutively expressed on NK cells and its expression correlates with sequential phases in NK-cell development, discriminating phenotypically and functionally different subsets within the NK-cell population. Although CD27 has been described to have an important regulatory role in effector and memory T and B lymphocytes, its role in NK-cell biology remains to be addressed. In this study, we used CD27(-/-) mice to investigate the role of CD27 in NK-cell development and function, both during the resting state and upon stimulation. The results show that NK-cell numbers are not impaired in CD27(-/-) mice. Moreover, CD27(-/-) NK cells reach full phenotypic maturity, evidenced by normal expression of CD49b, CD43 and CD11b. Expression of activating receptors is unaltered, whereas expression of several inhibitory receptors is increased. Cytotoxicity and interferon-γ production by NK cells from CD27(-/-) mice in the resting state are normal. However, upon in vivo anti-CD40- or poly-I:C-mediated activation, or in vitro interleukin-15 priming plus anti-NKp46 stimulation, the absence of CD27 results in decreased cytolytic activity and cytokine production by spleen and liver NK cells. In conclusion, this study demonstrates that CD27 is dispensable for the development of functional NK cells. However, upon stimulation of NK cells, CD27 displays an important role in their activation and functionality.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: De Colvenaer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Taveirne
authors.forename: Maarten
authors.initials: M
authors.lastname: Delforche
authors.forename: Magda
authors.initials: M
authors.lastname: De Smedt
authors.forename: Bart
authors.initials: B
authors.lastname: Vandekerckhove
authors.forename: Tom
authors.initials: T
authors.lastname: Taghon
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000276:immunology; D039481:CD11b Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D039421:Integrin alpha2 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051917:Leukosialin / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D039481:CD11b Antigen; D019013:CD40 Antigens; D016207:Cytokines; D039421:Integrin alpha2; D019409:Interleukin-15; D051917:Leukosialin; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma; D011070:Poly I-C