Correlation between natural cytotoxicity receptors and intracellular cytokine expression of peripheral blood NK cells in women with recurrent pregnancy losses and implantation failures.

PROBLEM: Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell cytotoxicity and cytokine production. We investigated whether women with recurrent pregnancy losses (RPLs) and implantation failures have aberrant correlation between NCRs and intracellular cytokine expression of NK cells.

METHOD OF STUDY: Peripheral blood NK cells (CD56(dim) and CD56(bright)) were analyzed for NCRs (NKp46, NKp44 and NKp30) and cytokine expression (TNF-alpha, IFN-gamma, IL-4, IL-10) using flow cytometry in RPL (n = 22), implantation failures (n = 23) or controls (n = 15).

RESULTS: In type 1 cytokine studies, CD56(bright)/NKp30(+) cells in controls (r = 0.696, P < 0.05) were positively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(+) cells. CD56(bright)/NKp46(+) cells in implantation failures (r = -0.76, P < 0.01) were negatively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(-) cells. RPL did not have any correlation. In type 2 cytokine studies, CD56(+)/NKp46(+) cells (r = 0.758, P < 0.01) and CD56(+)/NKp30(+) cells (r = 0.637, P < 0.05) were positively correlated with CD56(bright)/IL-4(+)/IL-10(+) cells in controls. CD56(+)/NKp30(+) cells in implantation failures (r = -0.778, P < 0.05) were negatively correlated with CD56(bright)/IL-10(+)/IL-4(+) cells. There were no correlations in RPL.

CONCLUSION: Recurrent pregnancy losses and implantation failures have lack of, or negative correlation between NCRs and intracellular cytokines expression. This observation suggests that excessive pro-inflammatory cytokine expression in NK cells in RPL and implantation failures may be exerted through the NCRs or interruption of signal transduction processes.