Back to Search
Start Over
CD56brightCD16- NK cells produce adenosine through a CD38-mediated pathway and act as regulatory cells inhibiting autologous CD4+ T cell proliferation
- Publication Year :
- 2015
-
Abstract
- Recent studies suggested that human CD56brightCD16− NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56dimCD16+ and CD56brightCD16− NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56brightCD16− than in CD56dimCD16+ NK cells. CD57 was mostly expressed by CD56dimCD16+ NK cells. CD203a/PC-1 expression was restricted to CD56brightCD16− NK cells. CD56brightCD16− NK cells produce ADO and inhibit autologous CD4+ T cell proliferation. Such inhibition was 1) reverted pretreating CD56brightCD16− NK cells with a CD38 inhibitor and 2) increased pretreating CD56brightCD16− NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56brightCD16− NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4+ T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56brightCD16− NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56brightCD16− NK cells act as “regulatory cells” through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune/inflammatory diseases.
- Subjects :
- CD4-Positive T-Lymphocytes
5'-Nucleotidase
ADP-ribosyl Cyclase
Adenosine
Antigens, CD
Antigens, CD38
Antigens, CD56
Antigens, CD57
Apyrase
Arthritis, Juvenile
Cell Proliferation
GPI-Linked Proteins
Humans
Killer Cells, Natural
Lymphocyte Activation
Membrane Glycoproteins
Receptors, IgG
Synovial Fluid
Immunology
Medicine (all)
Tolerance/Suppression/Anergy
Juvenile
Autoimmunity
CD38
Natural Killer Cells, Autoimmunity, Human, Tolerance/Suppression/Anergy
CD49b
5'-nucleotidase
Interleukin 21
CD57 Antigens
Receptors
Immunology and Allergy
Killer Cells
Janus kinase 3
CD56 Antigen
CD
Natural Killer Cells
medicine.anatomical_structure
Interleukin 12
Natural
CD56
CD57
Human
IgG
T cell
Biology
Immune system
medicine
Antigens
Arthritis
ADP-ribosyl Cyclase 1
Cancer research
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....cd771a8db0a0cabd05e4c708a80e7223