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2018 ; 9
(ä): 1429
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Primary Immunodeficiencies Unravel the Role of IL-2/CD25/STAT5b in Human Natural
Killer Cell Maturation
#MMPMID29988287
Caldirola MS
; Rodríguez Broggi MG
; Gaillard MI
; Bezrodnik L
; Zwirner NW
Front Immunol
2018[]; 9
(ä): 1429
PMID29988287
show ga
Natural killer (NK) cells play a pivotal role during immunity against viruses and
circumstantial evidence also indicates that they can protect the host against
developing tumors. Peripheral blood NK cells comprise CD56(bright)CD16(lo/-)
cells that constitutively express CD25 (IL-2R?) and CD56(dim)CD16(hi) cells that
express CD25 upon activation. Using NK cells from two patients, one with a
primary immunodeficiency characterized by a homozygous mutation in CD25 (born in
year 2007 and studied since she was 3?years old) and one with a homozygous
mutation in STAT5b (born in year 1992 and studied since she was 10?years old), we
observed that the absence of IL-2 signaling through CD25 promotes the
accumulation of CD56(bright)CD16(high) NK cells, and that CD56(bright)CD16(lo),
CD56(bright)CD16(high), and CD56(dim)CD16(high) NK cells of this patient
exhibited higher content of perforin and granzyme B, and proliferation capacity,
compared to healthy donors. Also, CD56(bright) and CD56(dim) NK cells of this
patient exhibited a reduced IFN-? production in response to cytokine stimulation
and increased degranulation against K562 cells. Also, the CD25-deficient patient
presented a lower frequency of terminally differentiated NK cells in the
CD56(dim)CD16(hi) NK subpopulation compared to the HD (assessed by CD57 and CD94
expression). Remarkably, CD56(dim)CD16(high) NK cells from both patients
exhibited notoriously higher expression of CD62L compared to HD, suggesting that
in the absence of IL-2 signaling through CD25 and STAT5b, NK cells fail to
properly downregulate CD62L during their transition from CD56(bright)CD16(lo/-)
to CD56(dim)CD16(hi) cells. Thus, we provide the first demonstration about the in
vivo requirement of the integrity of the IL-2/CD25/STAT5b axis for proper human
NK cell maturation.
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