HISTOLOGICAL STUDIES OF GENE-ABLATED MICE SUPPORT IMPORTANT FUNCTIONAL ROLES FOR NATURAL-KILLER-CELLS IN THE UTERUS DURING PREGNANCY

Maternal lymphocytes having a large and granulated morphology accumula te at healthy implantation sites in normal mice. Insight into the func tions of these cells has come from a previous study of two independent lines of mice deficient in natural killer (NK) cells. In pregnant Tg epsilon 26 mice, vascular pathology was found that led to the major co mplications of either fetal death or intrauterine growth retardation. In pregnant p56(lck) null x IL-2R beta null mice, extensive distension of the decidua was observed that separated the placenta from the myom etrium and appeared to be interstitial edema. To strengthen assignment of uterine large granulated lymphocytes to the NK cell lineage and to understand which aspects of NK cell biology may be important for a ut erine-based, pregnancy-associated subset, mid-gestation implantation s ites from a new series of mice having gene deletions which alter NK ce lls (IL-2R gamma null, Stat4 null, IL-12 p40 null, beta(7) integrin nu ll and Muc-1 null) have been examined histologically. The findings sup port the assignment of pregnancy-associated large granulated cells of mice to the NK cell lineage and suggest that the primary functions of these tissue-based NK cells are to support normal development of the d ecidua and/or its vasculature using pathways that involve IL-12 mediat ed signal transduction. (C) 1997 Elsevier Science Ireland Ltd.