Accentuated hypo- and hyper-NK lymphocyte CD8 expression is a marker of NK subsets' misbalance and is predictive for reproductive failures

Abstract

Introduction: NK cells play critical yet poorly defined role in reproductive processes. Role of CD8αα expression on a part of peripheral blood NK lymphocyte population is not clear.

Patients and methods: During isolated double-blinded clinical investigation we studied blood samples from 153 women with multiple reproductive failures undergoing IVF which were drawn 5-12d before embryo transfer procedure. 90 women had IVF failures (IVFf), 24 became pregnant with subsequent pregnancy failure (Pf), 39 became pregnant with subsequent successful pregnancy. During retrospective study we analyzed our laboratory data of 1045 infertile women which underwent routine immunology investigation after IVF failures. Lymphocyte phenotype and NK cytotoxicity was studied by FACScan flow cytometer using BD monoclonal abs.

Results: We showed that NK-CD8 expression being increased↑ (>60%) was predictive for IVFf (OR 3.523, p=0.0193, n=23) while being decreased↓ (<40%) was significantly predictive for subsequent Pf (OR 4.571, p=0.0418, n=37). Balanced "conditionally normal" NKCD8 expression (40-60%, n=93) was very significantly predictive for whole reproductive success after IVF (OR 3.972, p=0.0021). Analysing retrospective data, we found decreased CD3- CD56++ and T lymphocyte frequency in both "accentuated" groups compared to patients with "conditionally normal" NK-CD8 expression (n=562). NK-CD8 expression↓ (n=341) was associated with elevated HLADR expression on NK, CD3+, CD3+ CD8+, CD3+ CD4+ cells. Meanwhile, NK-CD8 expression ↑ (n=142) was associated with elevated NK frequency, NK cytotoxicity levels and CD158a expression on NK cells, simultaneously with decreased CD3CD8 and CD3+ CD56+ numbers.

Conclusion: Both hypo- and hyper-NK lymphocyte CD8 expression "accentuations" associated with NK subsets' misbalance (NK and T lymphocyte phenotype and cytotoxicity). Both hypo- and hyper-NK lymphocyte CD8 expression "accentuations" associated with poor IVF outcome, possibly through their association with other unfavorable accentuated parameters that result into unfavorable combination of "accentuated phenotype".

Keywords: CD8 expression on NK; CD8αα; Embryo implantation; NK activity; Natural killer lymphocytes.