Are natural killer cells distributed in relationship to nerve fibers in the pregnant mouse uterus?

Specialized lymphocytes, called uterine Natural Killer (uNK) cells, appear in human and rodent uteri and become abundant at implantation sites during decidualization and early pregnancy. The hallmark of human uNK cells is intense expression of CD56, a neural cell adhesion glycoprotein (NCAM-1) while mature (granulated) mouse uNK cells express asialoGM1, a brain ganglioside. Murine uNK cells initiate the normal structural changes induced in maternal spiral arteries by pregnancy but regulation of their recruitment, localization and activation is incompletely understood. To address whether uNK cell distribution is co-localized with nerve fiber distribution, sections of gestation day (gd) 6-12 implantation sites from C57BL/6 (B6) mice were studied. Nerve fibers reactive with antibodies to pan neurofilament 150 kD or with tyrosine hydroxylase, an enzyme restricted to sympathetic fibers, were present the walls of branches from the uterine artery in the mesentery. Reactivity was lost as the vessels crossed the myometrium and entered endometrium/decidua. Periodic Acid Schiffs reactive uNK cells were absent from the mesentery and enriched in decidua basalis where they transcribed NCAM-1 and associated with non-innervated segments of the uterine arteries, including spiral arteries. These data suggest that the localization and activation of mature uNK cells are unlikely to be neurotransmitter regulated.