Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 153

3.11.5.3 Interactions between NK Cells and Other Cell Types

The balance between cell death and coexistence results from stimulatory and
inhibitory signals delivered by plasmalemmal receptors. Natural killer cells are able
to discriminate abnormal cells from cells of their normal environment. NK cells are
tolerant to cells expressing MHC class-1 molecules. They circulate in blood vessels
and lymphatics and patrol into tissues to check possible presence of transformed or
infected cells that downregulate the expression of MHC class-1 molecules. NK cells
then form synapses with target cells.
NK cells directly or indirectly interact with dendritic, NKT, B, and CD4

T cells.
In addition, NK cells can inhibit or promote the activation of autoreactive T cells
during the initiation of autoimmunity [ 277 ]. NK cells are controlled by regulatory
T cells and can operate as regulators, as they can kill macrophages, dendritic cells,
and activated T and B lymphocytes and interact with endothelial cells.
Three NK-cell receptors promote adhesion to endothelial cells: (1)

+

α 4 β 1 -integrin
that binds VCAM1; (2) L-selectin that links to addressins; and (3) CX3CR1 that
associate with CX3CL1.
NK cells either cause vascular damage by killing endothelial cells or promote
angiogenesis in other circumstances, such as during pregnancy [ 282 ]. 158

NK cells

promote vascularization of embryos.

3.11.5.4 NK-Cell Precursors and Subpopulations

NK cells lodge in different tissue types. They are phenotypically and functionally
diverse. The NK-cell developmental niche with its set of stromal cells that secrete
growth factors can determine the fate of NK precursors.
Precursors of NK cells can differentiate into NK-effector subsets according to
the cytokine types. NK1 cells stimulated by IL12 produce Ifn

, whereas NK2 cells
stimulated by IL4 synthesize IL5 and IL13 [ 277 ]. NK1 cells kill target cells by a
process based on TNFRSF6a (or CD95), perforin, and granzyme. NK2 cells use a
mechanism that relies on TNFSF10 agent.
In humans, 2 populations of NK cells can be distinguished using CD56 marker,
a 140-kDa isoform of neural cell adhesion molecule (NCAM). NK cells indeed
comprise CD56 low and CD56 high subsets [ 282 ].
Most blood and spleen NK cells are CD56 low ,CD16

γ

+ (low-affinity receptor

for immunoglobulin-G, Fc γ R3) NK cells that are cytotoxic and produce CXCR1,

perforin, and Ifn ; they have enhanced killing activity. Excited with a proper

stimulus, CD56 low ,CD16

γ

+ NK cells synthesize abundantly cytokines.

158 During pregnancy, endometrium is enriched with uterine natural killer cells that correspond to
a specific subset of NK cells. They secrete vascular endothelial growth factor, placental growth
factor, and NKG5 to remodel the arterial network and support the placental development.