An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation.
The expansion of the cytokine-producing CD56(bright) NK cell subset is a main feature of lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated phenotypes and functions of CD56(bright) and CD56(dim) NK subsets from 43 HLA-matched non-T cell-depleted HSCT donor-recipient pairs. The early expansion of CD56(bright) NK cells gradually declined in the posttransplant period but still persisted for at least 1 year and was characterized by the emergence of an unusual CD56(bright)CD16(low) subset with an intermediate maturation profile. The activating receptors NKG2D and NKp46, but also the inhibitory receptor NKG2A, were overexpressed compared with donor CD56(bright) populations. Recipient CD56(bright) NK cells produced higher amounts of IFN-gamma than did their respective donors and were competent for degranulation. Intracellular perforin content was increased in CD56(bright) NK cells as well as in T cells compared with donors. IL-15, the levels of which were increased in the posttransplant period, is a major candidate to mediate these changes. IL-15 serum levels and intracellular T cell perforin were significantly higher in recipients with acute graft-vs-host disease. Altogether, CD56(bright) NK cells postallogeneic HSCT exhibit peculiar phenotypic and functional properties. Functional interactions between this subset and T cells may be important in shaping the immune response after HSCT.
Dulphy
Nicolas
N
Institut National de la Santé et de la Recherche Médicale, U662, Paris, France. nicolas.dulphy@univ-paris-diderot.fr
Haas
Philippe
P
Busson
Marc
M
Belhadj
Stéphanie
S
Peffault de Latour
Régis
R
Robin
Marie
M
Carmagnat
Maryvonnick
M
Loiseau
Pascale
P
Tamouza
Ryad
R
Scieux
Catherine
C
Rabian
Claire
C
Di Santo
James P
JP
Charron
Dominique
D
Janin
Anne
A
Socié
Gérard
G
Toubert
Antoine
A
D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D010641:Phenotype; D017452:Receptors, IgG / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
D019002:CD56 Antigen; D006680:HLA Antigens; D037102:Lectins; D017452:Receptors, IgG; D007371:Interferon-gamma; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins