Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques.
Interleukin-7 (IL-7), the principal cytokine implicated in thymopoiesis and peripheral T-cell homeostasis, is presently under evaluation in human diseases characterized by persistent lymphopenia. Unexpectedly, before the eventual IL-7-driven T-cell expansion, all treated patients showed a profound T-cell depletion 24 hours after injection. The current study uses the rhesus macaque model to investigate the mechanisms involved in this IL-7-induced T-cell depletion. We identify a new critical function of IL-7 that induces massive and rapid T-cell migration from the blood into various organs, including lymph nodes, parts of the intestine, and the skin. This homing process was initiated after the induction of chemokine receptor expression by circulating T cells and the production of corresponding chemokines in target organs. Finally, we demonstrate that the IL-7-induced cell cycling is initiated within these organs before T cells migrate back into the bloodstream, indicating that T-cell homing is required for in vivo IL-7 function.
Beq
Stéphanie
S
Département de Virologie, Institut Pasteur, 25-28 Rue du Docteur Roux, Paris Cedex 15, France.
Rozlan
Sandra
S
Gautier
David
D
Parker
Raphaëlle
R
Mersseman
Véronique
V
Schilte
Clémentine
C
Assouline
Brigitte
B
Rancé
Iann
I
Lavedan
Pascal
P
Morre
Michel
M
Cheynier
Rémi
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006031:Glycosylation; D007267:Injections; D015851:Interleukin-7 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D015851:Interleukin-7; D019707:Receptors, Chemokine; D011994:Recombinant Proteins