CD56bright cells increase expression of α4 integrin at ovulation in fertile cycles

Leukocyte content of human endometrium changes rapidly after ovulation, particularly as a result of gains in CD56(bright) uterine NK (uNK) cells. We have proposed that uNK precursor cells are found within the blood CD56(bright) pool and are recruited to decidualizing endometrium through functional changes in their adhesion molecules and chemokine receptors. This study sought to quantify alterations in adhesion molecules, cytokines, chemokines, and receptors induced in circulating CD56(+) cells of fertile and infertile women by ovulation. Blood was drawn from 12 fertile volunteers and six female- infertility patients at Menstrual Cycle Day (d) 5 and on the day following the preovulatory surge of luteinizing hormone (LH). CD56(bright), CD56(dim), and CD56(+)CD3(+) cell subsets were isolated and evaluated by flow cytometry, quantitative PCR, or Western blotting. In CD56(bright) cells from fertile but not infertile women, alpha(4) integrin increased between d5 and the preovulatory LH surge. CD56(dim) and NKT cells did not show a change in alpha(4) integrin but differed significantly between fertile and infertile donors, and infertile donors had reduced homing molecule expression in CD56(dim) and NKT cells, and at ovulation, their NKT cells showed elevated cytokine production. None of the circulating CD56(+) cell subsets had transcripts for receptors for estrogen, progesterone, LH, or prolactin. Thus, immunological events associated with the LH surge induce alterations in all subsets of CD56(+) cells, and the unique induction of alpha(4) integrin in CD56(bright) cells of fertile women constitutes a potential method to promote uterine homing.