Transplantation into genetically alymphoid mice as an approach to dissect the roles of uterine natural killer cells during pregnancy--a review.
Mice genetically deficient in the natural killer (NK) cell lineage lack uterine (uNK cells) and demonstrate morphometrically-quantifiable histopathology within their implantation sites. Two particular mouse strains, tg(epsilon),26 and RAG-2 null x gamma(c) null, have been used successfully as transplant recipients to address questions relating to the biology of uNK cells. uNK cells did not differentiate within decidualized uterine graft segments from normal mice, which were anastomosed orthotopically into immunodeficient hosts. uNK cells did appear in similar grafts placed into immunocompetent hosts, indicating that uNK cells or their progenitors must home to the uterus. This was confirmed by splenocyte transplantation into pregnant uNK cell deficient recipients. Only splenocytes from pregnant donors, not those from non-pregnant donors, homed to the uterus. Homing in this in vivo assay was independent of the CC-chemokine receptors, CCR-2 and CCR-5. Longer-term bone marrow cell reconstitution of neonatal or virgin adult uNK cell-deficient mice has identified a functional role for uNK cells in modification of the decidual arterioles which is mediated by IFN-gamma. By utilizing mutant and gene-ablated mice as donors for tissue or haematopoietic cell transplants to uNK cell deficient mice, it should be possible to fully characterize the in vivo regulation and functions of these pregnancy-specific uterine lymphocytes.
Croy
B A
BA
Department of Biomedical Sciences, University of Guelph, Ontario, Canada. acroy@uoguelph.ca
Di Santo
J P
JP
Greenwood
J D
JD
Chantakru
S
S
Ashkar
A A
AA
D000818:Animals; D002465:Cell Movement; D010064:Embryo Implantation / Q000276:immunology; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014599:Uterus / Q000166:cytology / Q000276:immunology* / Q000637:transplantation