Korean J Obstet Gynecol.  2012 Oct;55(10):713-720.

Changes of natural killer cell number and cytolytic activity during first trimester of pregnancy in recurrent spontaneous abortion patients and fertile control

• Kim YH
• Kim YJ
• Jeong SO
• Cha SH
• Choi MH
• Yang KM

Abstract

OBJECTIVE
We aimed to evaluate whether natural killer cell (NK cell) numbers and their cytolytic activity are changed in 1st trimester of pregnancy in patients who had history of recurrent spontaneous abortion (RSA).
METHODS
Non-pregnant women who had history of RSA (n=48) and 10 patients who had success to get pregnancy comprised the study group. Non-pregnant fertile (n=17) and early pregnant women (n=7) who had history of at least one term birth without history of RSA or infertility were included as controls. %NK cells among peripheral blood lymphocyte and their cytolytic activities are measured.
RESULTS
%NK cells among peripheral blood lymphocyte in RSA patients before pregnancy was significantly higher than that of non-pregnant normal control. NK cell cytolytic activity in non-pregnant RSA patients was significantly higher than that of non-pregnant fertile group. After success to get pregnancy, NK cell cytolytic activity in RSA patients were decreased but were not significantly different compared to that of NK cell cytolytic activity checked at non-pregnant status. NK cell cytolytic activity in pregnant RSA patients was significantly higher than that of pregnant normal control.
CONCLUSION
Failure to decrease NK cell cytolytic activity in early pregnancy would have pivotal role in failure to sustain pregnancy in RSA patients. Further studies would be needed for clarifying our results.

Keyword

Recurrent spontaneous abortion; Peripheral blood natural killer cell; Natural killer cell cytolytic activity

MeSH Terms

Abortion, Spontaneous
Female
Humans
Infertility
Killer Cells, Natural
Lymphocytes
Pregnancy
Pregnancy Trimester, First
Pregnant Women
Term Birth

Figure

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  Fig. 1 Determination of immune cell profiles in peripheral blood. Gating strategy for three color flow cytometry evaluation of peripheral blood immune cell. This step descript of analysis gate around lymphocyte (R1), excluding cell debris (A). Next step shows four regions as NK cell, CD3-/16+/56+ (B), NKT cell, CD3+/16+/56+, T cell, CD3+/56- and B cell (CD3-/56-) each. SCC, squamous cell carcinoma; NK cell, natural killer cell.

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  Fig. 2 Determination of peripheral blood natural killer cell (NK cell) cytolytic activities. Figures describes analysis gate around K562 (target cell) live & dead cell in control (A, no effector cell), 50:1 E:T ratio (B), 25:1 E:T ratio (C), and 12.5:1 E:T ratio (D) each which excluding cell debris. E:T, effector cell:target cell; PI, propidum iodie dye.

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  Fig. 3 Comparisons of natural killer cell (NK cell) levels (%) between recurrent spontaneous abortion (RSA) and normal control. aP-value<0.05.

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  Fig. 4 Comparision of natural killer cell (NK cell) cytolytic activity between recurrent spontaneous abortion (RSA) and fertile group. E:T ratio is (A) 50:1, (B) 25:1, (C) 12.5:1. aP-value<0.05.

Reference

1. Hannes M, Englert Y, Gotlieb W, Dupont E. Recurrent spontaneous miscarriage. Rev Med Brux. 1992. 13:103–106.

2. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol. 1984. 148:140–146.

3. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996. 17:138–146.

4. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, et al. Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol. 1996. 106:127–133.

5. Perricone R, De Carolis C, Kroegler B, Greco E, Giacomelli R, Cipriani P, et al. Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion. Rheumatology (Oxford). 2008. 47:646–651.

6. Kwak JY, Beaman KD, Gilman-Sachs A, Ruiz JE, Schewitz D, Beer AE. Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. Am J Reprod Immunol. 1995. 34:93–99.

7. Hussain MJ, Alviggi L, Millward BA, Leslie RD, Pyke DA, Vergani D. Evidence that the reduced number of natural killer cells in type 1 (insulin-dependent) diabetes may be genetically determined. Diabetologia. 1987. 30:907–911.

8. Higuchi K, Aoki K, Kimbara T, Hosoi N, Yamamoto T, Okada H. Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters. Am J Reprod Immunol. 1995. 33:221–227.

9. King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010. 25:52–58.

10. Aoki K, Kajiura S, Matsumoto Y, Ogasawara M, Okada S, Yagami Y, et al. Preconceptional natural-killer-cell activity as a predictor of miscarriage. Lancet. 1995. 345:1340–1342.

11. Rezaei A, Dabbagh A. T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Med Sci Monit. 2002. 8:CR607–CR610.

12. Vassiliadou N, Bulmer JN. Functional studies of human decidua in spontaneous early pregnancy loss: effect of soluble factors and purified CD56+ lymphocytes on killing of natural killer- and lymphokine-activated killer-sensitive targets. Biol Reprod. 1998. 58:982–987.

13. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001. 22:633–640.

14. Lanier LL, Le AM, Ding A, Evans EL, Krensky AM, Clayberger C, et al. Expression of Leu-19 (NKH-1) antigen on IL 2-dependent cytotoxic and non-cytotoxic T cell lines. J Immunol. 1987. 138:2019–2023.

15. Lachapelle MH, Miron P, Hemmings R, Roy DC. Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol. 1996. 156:4027–4034.

16. Emmer PM, Veerhoek M, Nelen WL, Steegers EA, Joosten I. Natural killer cell reactivity and HLA-G in recurrent spontaneous abortion. Transplant Proc. 1999. 31:1838–1840.