NK cell maturation and peripheral homeostasis is associated with KLRG1 up-regulation.
NK cells are important for the clearance of tumors, parasites, and virus-infected cells. Thus, factors that control NK cell numbers and function are critical for the innate immune response. A subset of NK cells express the inhibitory killer cell lectin-like receptor G1 (KLRG1). In this study, we identify that KLRG1 expression is acquired during periods of NK cell division such as development and homeostatic proliferation. KLRG1(+) NK cells are mature in phenotype, and we show for the first time that these cells have a slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. Transfer into lymphopenic recipients indicate that KLRG1(-) NK cells are precursors of KLRG1(+) NK cells and KLRG1 expression accumulates following cell division. Furthermore, KLRG1(+) NK cells represent a significantly greater proportion of NK cells in mice with enhanced NK cell numbers such as Cd45(-/-) mice. These data indicate that NK cells acquire KLRG1 on their surface during development, and this expression correlates with functional distinctions from other peripheral NK cells in vivo.
Huntington
Nicholas D
ND
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. nhunting@pasteur.fr
Tabarias
Hy
H
Fairfax
Kirsten
K
Brady
Jason
J
Hayakawa
Yoshihiro
Y
Degli-Esposti
Mariapia A
MA
Smyth
Mark J
MJ
Tarlinton
David M
DM
Nutt
Stephen L
SL
D000818:Animals; D006706:Homeostasis; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D015854:Up-Regulation
D020382:Interleukin-18; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018664:Interleukin-12; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse