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 ute rine (uNK cells) and demonstrate morphometrically-quantifiable histopatholo gy within their implantation sites. Two particular mouse strains, tg epsilo n,26 and RAG-2 null x gamma c null, have been used successfully as transpla nt recipients to address questions relating to the biology of uNK cells. uN K cells did not differentiate within decidualized uterine graft segments fr om normal mice, which were anastomosed orthotopically into immunodeficient hosts. uNK cells did appear in similar grafts placed into immunocompetent h osts, indicating that uNK cells or their progenitors must home to the uteru s. 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 bo ne marrow cell reconstitution of neonatal or virgin adult uNK cell-deficien t mice has identified a functional role for uNK cells in modification of th e decidual arterioles which is mediated by IFN-gamma. By utilizing mutant a nd gene-ablated mice as donors for tissue or haematopoietic cell transplant s to uNK cell deficient mice, it should be possible to fully characterize t he in vivo regulation and functions of these pregnancy-specific uterine lym phocytes. (C) 2000 IFPA and Harcourt Publishers Ltd.