en فعالیت سیتوتوکسیک سلول های تک هسته ای خون محیطی در بیماران مبتلا به آندومتریوز: یک مطالعه مقطعی Cellular and Molecular Biology of Reproduction Original Article Original Article <div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">اعتقاد بر این است که آندومتریوز با اختلال عملکرد سلول&shy;های لنفوسیتی و سمیت سلولی سلول‌های کشنده طبیعی (</span></span><span dir="LTR" style="font-size:10.0pt">NK</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، تحریک</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">شده ناشی از تولید اینترلوکین-2 (</span></span><span dir="LTR" style="font-size:10.0pt">IL-2</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) مرتبط است.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">این مطالعه با هدف بررسی فعالیت لنفوسیت&shy;های </span></span><span dir="LTR" style="font-size:10.0pt">T</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و سلول&shy;های </span></span><span dir="LTR" style="font-size:10.0pt">NK</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در سلول</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های تک</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">هسته</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">ای خون محیطی (</span></span><span dir="LTR" style="font-size:10.0pt">PBMCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) زنان مبتلا به آندومتریوز انجام شد.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مواد و روش&shy;ها: </span></span></b><span dir="LTR" style="font-size:10.0pt">PBMCs</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">از نمونه‌های خون وریدی محیطی 14 زن مبتلا به آندومتریوز و بدون آندومتریوز (7 نفر برای هر گروه) تهیه شد. سپس، &nbsp;&nbsp;&nbsp;</span></span><span dir="LTR" style="font-size:10.0pt">PBMC</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">ها به مدت 4 روز به طور همزمان کشت شدند و با </span></span><span dir="LTR" style="font-size:10.0pt">IL-2</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نوترکیب برای فعالیت سیتوتوکسیک به سمت سلول&shy;های هدف (سلول&shy;های </span></span><span dir="LTR" style="font-size:10.0pt">Daudi</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و </span></span><span dir="LTR" style="font-size:10.0pt">K562</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) تیمار شدند. فعالیت سمیت سلولی با استفاده از روش آزادسازی کرومیوم 51 قبل و بعد از تحریک تعیین شد. اندازه</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">گیری فلوسیتومتری برای بررسی بیان لنفوسیت&shy;های </span></span><span dir="LTR" style="font-size:10.0pt">T</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و سلول&shy;های </span></span><span dir="LTR" style="font-size:10.0pt">NK</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> قبل و بعد از درمان با </span></span><span dir="LTR" style="font-size:10.0pt">IL-2</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">استفاده شد.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">غلظت </span></span><span lang="FA" style="font-size:10.0pt">+</span><span dir="LTR" style="font-size:10.0pt">CD3+CD28</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> (هم‌تحریکی) در گروه آندومتریوز (38/5</span></span> <span lang="FA" style="font-size:10.0pt">&plusmn;</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">62/65) در مقایسه با همتای خود (22/4</span></span> <span lang="FA" style="font-size:10.0pt">&plusmn;</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 24/50) (04/0 </span></span><span lang="FA" style="font-size:10.0pt">= </span><span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) قبل از تحریک &nbsp;&nbsp;به ‌طور معنی‌داری کمتر بود. با این حال، تفاوت معنی</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">داری در سایر لنفوسیت</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">T</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و سلول</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">NK</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> مشاهده نشد. همچنین مشخص شد که افزایش قابل توجهی در </span></span><span lang="FA" style="font-size:10.0pt">+</span><span dir="LTR" style="font-size:10.0pt">CD3-CD28</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> پس از درمان با </span></span><span dir="LTR" style="font-size:10.0pt">IL-2</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">تنها در افراد سالم وجود دارد در حالیکه این افزایش در زنان مبتلا به آندومتریوز وجود نداشت.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتیجه&shy;گیری:</span></span></b> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">افزایش بیان </span></span><span dir="LTR" style="font-size:10.0pt">CD160</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و کاهش </span></span><span dir="LTR" style="font-size:10.0pt">CD28</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مهار فعال‌سازی سلول‌های </span></span><span dir="LTR" style="font-size:10.0pt">NK</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و پاسخ سلول‌های </span></span><span dir="LTR" style="font-size:10.0pt">T</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در زنان مبتلا به آندومتریوز نقش دارد.</span></span></span></span></span></span></span><br> <br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">کلمات کلیدی:</span></span></i></b> <i><span dir="LTR" style="font-size:9.0pt">CD28</span></i><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">، </span></span></i><i><span dir="LTR" style="font-size:9.0pt">CD160</span></i><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">، سیتوتوکسیک، آندومتریوز، </span></span></i><i><span dir="LTR" style="font-size:9.0pt">PBMC</span></i><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">.</span></span></i></span></span></span></span></span></div> <div style="text-align: justify;"><span style="font-size:12pt"><span sans-serif="" style="font-family:Calibri,"><b><span new="" roman="" style="font-family:" times="">Background:</span></b><span new="" roman="" style="font-family:" times=""> Endometriosis is believed to be associated with dysfunction of the lymphocyte population and cytotoxicity of natural killer (NK) cells, induced by the production of interleukin-2 (IL-2).</span></span></span><br> <span style="font-size:12pt"><span sans-serif="" style="font-family:Calibri,"><b><span new="" roman="" style="font-family:" times="">Objective:</span></b><span new="" roman="" style="font-family:" times=""> This study aimed to investigate T lymphocytes and NK cell activity in the peripheral blood mononuclear cells (PBMCs) of women with endometriosis.</span></span></span><br> <span style="font-size:12pt"><span sans-serif="" style="font-family:Calibri,"><b><span new="" roman="" style="font-family:" times="">Materials and Methods:</span></b><span new="" roman="" style="font-family:" times=""> PBMCs were obtained from the peripheral venous blood samples of 14 women with and without endometriosis (</span><span lang="EN-ID" new="" roman="" style="font-family:" times="">n = 7 for each group</span><span new="" roman="" style="font-family:" times="">). Then, the PBMCs were co-cultured for 4 days and were treated with recombinant IL-2 for cytotoxic activity toward target cells (Daudi and K562 cells). The cytotoxicity activity was determined using the 51 chromium release assay before and after stimulation. Flow cytometry measurement was used to examine the expression of &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;T lymphocytes and NK cells before and after being treated with IL-2.</span><span lang="EN-ID" style="font-family:"Times New Roman","serif""></span></span></span><br> <span style="font-size:12pt"><span sans-serif="" style="font-family:Calibri,"><b><span new="" roman="" style="font-family:" times="">Results:</span></b><span new="" roman="" style="font-family:" times=""> The concentration of CD3+CD28+ (co-stimulatory) was significantly lower in the endometriosis group (65.62 &plusmn; 5.38) compared to in its counterpart (50.24 &plusmn; 4.22) (p = 0.04) before stimulation. However, no significant differences were observed in any other T lymphocytes and NK cells. It was also found that there was a significant increase of CD3-CD28+ after treatment with IL-2 only in the healthy control but not in women with endometriosis.</span></span></span><br> <span style="font-size:12pt"><span sans-serif="" style="font-family:Calibri,"><b><span new="" roman="" style="font-family:" times="">Conclusion:</span></b><span new="" roman="" style="font-family:" times=""> Increased expression of CD160 and decreased CD28 play a role in inhibiting NK cell activation and T cell response in women with endometriosis.</span></span></span></div> CD28, CD160, سیتوتوکسیک, آندومتریوز, PBMC. CD28, CD160, Cytotoxic, Endometriosis, PBMC. 691 700 http://ijrm.ir/browse.php?a_code=A-10-1505-4&slc_lang=en&sid=1 Raden Muharam rmuharam@yahoo.com 0000-0001-5712-3931 Yes Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. Arleni Bustami arleni.ab@gmail.com 0000-0001-9222-6610 No Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. Indra Gusti Mansur mansur.indra@gmail.com 0000-0001-9159-8842 No Biomedical Science Master Program, Faculty of Medicine, University of Indonesia Teuku Zulkifli Jacoeb tzjacoeb@gmail.com 0000-0001-9690-4415 No Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. Jerome Giustiniani jerome.giustiniani@gmail.com 0000-0002-4612-0759 No INSERM U976, Saint-Louis Hospital-Paris VII, Paris, France. Valerie Schiavon valerie.schiavon@inserm.fr 0000-0001-8466-774X No INSERM U976, Saint-Louis Hospital-Paris VII, Paris, France. Armand Bensussan armand.bensussan@inserm.fr 0000-0002-0409-2497 No INSERM U976, Saint-Louis Hospital-Paris VII, Paris, France. Mohammed VI-Polytechnic University, Ben Guerir, Morocco.