Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium

Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR

doi:10.1016/s0015-0282(16)54414-8

Fertility and Sterility, 56(1), 45-51, 1991

Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium

Freddy Cornillie , P R Koninckx , D J Oosterlynck

Author affiliations

Rega Institute for Medical Research ROR

DOI10.1016/s0015-0282(16)54414-8 PMID2065804

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Abstract

Objective

The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated.

DESIGN, SETTING,

Patients

Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly.

Main Outcome Measure

The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells.

Results

The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present.

Conclusion

The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.

Topics

Endometriosis > Pathophysiology > Immune Dysfunction Endometriosis > Immunology > Natural Killer Cell Activity Infertility > Endometriosis-Related > Immune Mechanisms

natural killer cell defect endometriosis cytotoxicity, NK cell activity decreased endometriosis autologous endometrium, cellular immunity endometriosis natural killer cells infertility, Oosterlynck Koninckx NK cytotoxicity endometriosis severity, endometrial cell resistance NK cell killing endometriosis, anti-Leu-11b monoclonal antibody NK cell mediated cytotoxicity, K562 assay NK activity women with endometriosis, immune dysfunction endometriosis pathogenesis implantation, decreased cellular immunity endometriosis disease severity correlation, endometriosis immunology NK cell deficiency prospective study

PMID 2065804 2065804 DOI 10.1016/s0015-0282(16)54414-8 10.1016/s0015-0282(16)54414-8

Cite this article

Oosterlynck, D. J., Cornillie, F. J., Waer, M., Vandeputte, M., & Koninckx, P. R. (1991). Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertility and sterility, 56(1), 45-51. https://doi.org/10.1016/s0015-0282(16)54414-8

Keywords

Chromium Radioisotopes, Cytotoxicity, Immunologic, Endometriosis/immunology/pathology, Endometrium/immunology/pathology, Female, Flow Cytometry, Humans, Immunity, Cellular, Killer Cells, Natural/immunology/pathology, Leukocyte Count, Prospective Studies, Chromium Radioisotopes

EndometriosisNatural Killer Cell ActivityPeritoneal Fluid EnvironmentImmune Dysfunction

The natural killer activity of peritoneal fluid lymphocytes is decreased in women with endometriosis

Oosterlynck DJ et al., 1992Fertil Steril

To investigate the local natural killer (NK) activity of the peritoneal fluid mononuclear cells (PFMC). In a prospective way, the NK activity (K562-assay) was measured in peripheral blood (PB) and peritoneal fluid (PF) of 44 women who underwent a laparoscopy for infertility and/or pain at the University Hospital of Gasthuisberg, Leuven, Belgium. The NK activity of peripheral blood mononuclear cells and PFMC, the number and concentration of PFMC, the percentage of lymphocytes versus macrophages by May-Grünwald-Giemsa staining and the estradiol and progesterone concentration of the PF were correlated together and with the severity of endometriosis. We demonstrated that there is a significant NK activity in PF and that this activity is decreased in women with endometriosis. This defect was more pronounced in the follicular phase of the cycle compared with the postovulatory phase. In PB of the same 44 women, the decreased NK activity correlated with the severity of the disease. This confirms our previous report on another 34 women. The NK activity is decreased in women with endometriosis and correlated significantly with the severity of the disease in both the PB and PF of women with endometriosis.

EndometriosisEstrogen Receptor MechanismsBaboon ModelImmune Dysfunction

Future directions in endometriosis research

Hastings JM et al., 2003Semin Reprod Med

Endometriosis is an estrogen-dependent condition that affects 5 million American women; however, its etiology is not fully understood. The development of the baboon model of endometriosis provides an extremely powerful tool to investigate the development and progression of endometriosis from the early invasive phase to the advanced established disease. The inflammatory reaction that occurs in the peritoneal cavity at the site of endometriotic lesions does not clear the refluxed endometrial fragments. Moreover, this reaction appears to promote the survival of the tissue and the development of the disease. Exploration of the interactions between peritoneal macrophages and cytotoxic T cells and endometrial cells will determine whether their ability to scavenge and induce apoptosis is altered. Determining the mechanism(s) that induces the expression of estrogen and its receptor (ERbeta) is crucial to our understanding of the progression of the disease. The effects of ERbeta activation in endometriotic lesions should be investigated. It is important to determine the effects of estrogen on the function of the immune cells, either directly or indirectly. Finally, determining the effect of events at sites of ectopic endometrium on the eutopic endometrium may elucidate the mechanism(s) of infertility associated with endometriosis.

EndometriosisImmune DysfunctionCellular Immunity DeficiencyAutoimmune Response in Endometriosis

Deficient cellular immunity in endometriosis

Dmowski WP et al., 1981Am J Obstet Gynecol

Cell-mediated autoimmune responses were studied by means of in vivo and in vitro techniques in five rhesus monkeys with spontaneous endometriosis. The results were compared with similar data obtained from five normal rhesus monkeys without endometriosis. The in vivo studies included intrademal injection of autologous antigens prepared from uterine endometrium, ectopic endometrium, or peritoneum, or injection of the mitogen, phytohemagglutinin (PHA). Skin biopsies were obtained at 48 hours and evaluated under the light microscope for perivascular lymphocytic infiltration. The mean number of lymphocytes per high-power field after injection of the autologous endometrial antigen was significantly smaller in animals affected by endometriosis than in the control group. There was no significant difference in lymphocytic response to autologous peritoneal antigens between the groups. Animals of both groups responded readily to PHA with marked perivascular lymphocytic infiltration. Lymphocyte stimulation responses to the same autologous antigens or to PHA were evaluated by means of in vitro assays and micro-methods. Lymphocyte stimulation response to autologous endometrial antigens in the group with endometriosis was significantly less than in the control group. There was no significant difference in response to the peritoneal antigens between the groups, and the response to PHA was marked in all animals of both groups. The results of this study indicate that rhesus monkeys with spontaneous endometriosis have an altered cellular immune response to autologous antigens. Although the animals were immunologically competent, as judged by responses to PHA, both in vivo and in vitro studies indicated a decrease in the cell-mediated immune response to autologous endometrial antigens. These data suggest that endometrial cells translocated from their normal location may implant only in women with specific alteration in cell-mediated immunity. New light is thus shed on the cause of endometriosis.

Research

Recurrent pregnancy loss: a committee opinion

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Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium

Abstract

Topics

Cite this article

Keywords

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