1. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education
- Author
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Malin Flodström-Tullberg, Andreas T. Björklund, Karl-Johan Malmberg, Sandra Andersson, Jakob Michaëlsson, Martin E. Rottenberg, Frank Heuts, Peggy Riese, Martin A. Ivarsson, Niklas K. Björkström, Cyril Fauriat, Carlos A. Guzmán, and Hans-Gustaf Ljunggren
- Subjects
Cellular differentiation ,Transplantation, Heterologous ,Immunology ,In Vitro Techniques ,Biology ,Biochemistry ,Natural killer cell ,Mice ,CD57 Antigens ,Immune system ,Receptors, KIR ,medicine ,Animals ,Humans ,Cell Proliferation ,Mice, Knockout ,Mice, Inbred BALB C ,Lymphokine-activated killer cell ,Innate immune system ,Hematopoietic Stem Cell Transplantation ,Cell Differentiation ,Cell Biology ,Hematology ,CD56 Antigen ,Cell biology ,Killer Cells, Natural ,Phenotype ,medicine.anatomical_structure ,Neural cell adhesion molecule ,NK Cell Lectin-Like Receptor Subfamily C ,Homing (hematopoietic) - Abstract
Natural killer (NK) cells are lymphocytes of the innate immune system that, following differentiation from CD56bright to CD56dim cells, have been thought to retain fixed functional and phenotypic properties throughout their lifespan. In contrast to this notion, we here show that CD56dim NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57, change their expression patterns of homing molecules, and display a gradual decline in proliferative capacity. All cellular intermediates of this process are represented in varying proportions at steady state and appear, over time, during the reconstitution of the immune system, as demonstrated in humanized mice and in patients undergoing hematopoietic stem cell transplantation. CD56dim NK-cell differentiation, and the associated functional imprint, occurs independently of NK-cell education by interactions with self–human leukocyte antigen class I ligands and is an essential part of the formation of human NK-cell repertoires.
- Published
- 2010
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