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Problem Uterine natural killer (uNK) cells are enriched in the post-ovulatory uterus and during pregnancy. Whether these cells arise from blood pre-cursors or from stem cells in the uterus is undefined. To support a hypothesis that precursors of uNK cells are recruited from blood, adhesive function of blood CD56+ subsets were assessed during one cycle and during pregnancy. Method of study Fifteen women of proven fertility provided serial blood samples during one menstrual cycle and thirty women with a history of implantation failure or recurrent spontaneous abortion provided serial samples during infertility treatment. Results CD56bright cells, but not CD56dim cells or NKT cells, increased in ligand-binding capacity during ovulation in fertile cycles only and during the first 2 weeks from date of missed menses. Conclusion Enhanced adhesive function at ovulation in CD56bright cells in fertile cycles and during early gestation supports a hypothesis of recruitment of pre-uNK cells from the blood CD56bright subset. [ABSTRACT FROM AUTHOR]

Problem Patients with elevated blood natural killer (NK) cells may be offered intravenous immunoglobulin (IVIG) treatment, but there is controversy about the utility of blood NK cell testing. Human CD56+ NK cells include several subpopulations that include the putatively cytotoxic CD56+ CD16+ subset. In mouse models of pregnant failure, NKT cells appear to be important. However, a mouse model may only be pertinent to a subset of patients, as recurrent pregnancy failure is a heterogenous group. Method of study An ethics-approved observational study was done to observe the effect of treatment on total blood lymphoid cells, and subsets of CD56+ blood lymphocytes including CD56+ CD3+ NKT cells determined by flow cytometry, and to correlate with pregnancy outcome. Fifteen fertile women with a history of successful pregnancy and thirty-one women suffering from repeated implantation failure or recurrent spontaneous abortion provided serial blood samples during one menstrual cycle or prior to and during treatment. IVIG was administered to the latter group with or without heparin/aspirin. Results Eight of thirty infertile women presented with high numbers of CD56+ CD3+ NKT cells, which declined after treatment with IVIG. The elevated NKT cell group with or without concomitant autoimmunity achieved a significantly higher successful pregnancy rate over the course of the study, as compared to women with average numbers of NKT cells and no evidence of autoimmunity ( P = 0.018). Elevated NKT levels alone was an independent predictor of success on treatment ( P = 0.003). Conclusion Elevated NKT cells in recurrent pregnancy loss or implantation failure can be ameliorated with IVIG treatment, and result in successful pregnancy. Assay of NKT cell numbers may idengif"y patients who are more likely to benefit from IVIG therapy and merits further examination in randomized phase II studies. [ABSTRACT FROM AUTHOR]