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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1273-1281
IMMUNOBIOLOGY
Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin-5) cytokines at distinct stages of natural
killer cell differentiation from progenitor cells
Matthew J. Loza,
Loris Zamai,
Livio Azzoni,
Emanuela Rosati, and
Bice Perussia
From The Kimmel Cancer Center, Jefferson Medical
College, Philadelphia, PA.
To determine whether production of type 1 and type 2 cytokines
defines discrete stages of natural killer (NK) cell differentiation, cytokine expression was analyzed in human NK cells generated in vitro
in the presence of interleukin-15 (IL-15) and/or IL-2 from umbilical
cord blood hematopoietic progenitors. Like peripheral NK cells, the
CD161+/CD56+ NK cells from these cultures
contained a tumor necrosis factor alpha
(TNF- )+/granulocyte macrophage-colony-stimulating
factor (GM-CSF)+ subset, an interferon gamma
(IFN- )+ subset, mostly included within the former, and
very few IFN- /IL-13+ cells. Instead, most
immature CD161+/CD56 NK cells, detectable
only in the cultures with IL-2, produced IL-13, TNF- , and GM-CSF,
but not IFN- , and contained an IL-5+ subset. In
short-term cultures with IL-12 and feeder cells, a proportion of the
immature cells acquired the ability to produce IFN- . Part of these
produced both IFN- and IL-13, irrespective of induced CD56
expression. These in vitro data indicate that ability to produce the
type 2 cytokines IL-13 and IL-5 defines CD161+ NK cells at
intermediate stages of differentiation, and is lost upon terminal
functional differentiation, concomitant with acquired ability to
produce IFN- .

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