IL-7 enhances survival of human CD56bright NK cells.
Lymphoid differentiation and activation critically depend on cytokine stimulation and the interleukin-7 (IL-7) signaling in particular. Although it has been demonstrated that IL-7 may play a role in natural killer (NK) cell maturation, the effect of IL-7 stimulation on mature human NK cells has not been studied. We, therefore, investigated the expression and functional activity of IL-7Ralpha on mature NK populations from adult blood. In this article, we demonstrate that IL-7Ralpha is specifically expressed in the CD56bright noncytotoxic cytokine-producing NK subset. Importantly, this expression is thymus independent, contrary to what is observed in mice. In addition, we show that IL-7Ralpha is expressed at higher levels on NKG2A+CD56bright NK cells. In contrast to IL-15 stimulation, IL-7 does not increase NK cell cytotoxicity, interferon-gamma production, or the expression of activation markers, indicating that these cytokines play different functions in NK homeostasis and activation. However, IL-7 promotes the survival of the CD56bright NK subset and inhibits apoptosis by increasing BCL2 expression. These data should be taken into account when considering the clinical use of IL-7, particularly after stem cell transplantation.
Michaud
Annie
A
Groupe de Recherche En Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de cancérologie Charles Bruneau, Centre de recherche du CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
Dardari
R'Kia
R
Charrier
Emily
E
Cordeiro
Paulo
P
Herblot
Sabine
S
Duval
Michel
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019002:CD56 Antigen / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology
D019002:CD56 Antigen; D019409:Interleukin-15; D015851:Interleukin-7; D055654:NK Cell Lectin-Like Receptor Subfamily C; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma