Tissue Distribution Dynamics of Human NK Cells Inferred from Peripheral Blood Depletion Kinetics after Sphingosine-1-Phosphate Receptor Blockade.
Human natural killer (NK) cell subsets differentially distribute throughout the organism. While CD56(dim) and CD56(bright) NK cell subsets similarly reside in the bone marrow (BM), the CD56(dim) population predominantly accumulates in non-lymphoid tissues and the CD56(bright) counterpart in lymphoid tissue (LT). The dynamics with which these NK cell subsets redistribute to tissues remains unexplored. Here, we studied individuals newly exposed to fingolimod, a drug that efficiently blocks sphingosine-1-phosphate (S1P)-directed lymphocyte - including NK cell - egress from tissue to blood. During an observation period of 6h peripheral blood depletion of CD56(bright) NK cells was observed 3 h after first dose of fingolimod, with 40-50% depletion after 6 h, while a decrease of the numbers of CD56(dim) NK cells did not reach the level of statistical significance. In vitro, CD56(bright) and CD56(dim) NK cells responded comparably to the BM-homing chemokine CXCL12, while CD56(bright) NK cells migrated more efficiently in gradients of the LT-homing chemokines CCL19 and CCL21. In conjuncture with these in vitro studies, the indirectly observed subset-specific depletion kinetics from blood are compatible with preferential and more rapid redistribution of CD56(bright) NK cells from blood to peripheral tissue such as LT and possibly also the inflamed central nervous system. These data shed light on an unexplored level at which access of NK cells to LT, and thus, for example antigen-presenting cells, is regulated.
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.|Department of Neurology, University Hospital Basel, Basel, Switzerland.
M
M
Mehling
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
A-V
AV
Burgener
Department of Autoimmunity, Transplantation & Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland.
V
V
Brinkmann
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
G R
GR
Bantug
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
S
S
Dimeloe
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
G
G
Hoenger
Department of Neurology, University Hospital Basel, Basel, Switzerland.
L
L
Kappos
Immunobiology Laboratory/Department of Biomedicine and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
C
C
Hess
D000293:Adolescent; D000328:Adult; D000368:Aged; D001775:Blood Circulation; D001853:Bone Marrow / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D008221:Lymphoid Tissue / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000187:drug effects; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors*; D055815:Young Adult
D019002:CD56 Antigen; D018925:Chemokines; D007166:Immunosuppressive Agents; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride