NUMBERS OF NATURAL KILLERS LYMPHOCYTES DO NOT DETERMINE THEIR CYTOTOXICITY
DOI: http://dx.doi.org/10.30970/sbi.1302.599
Abstract
Natural killer’s cytotoxicity test accepted as a “gold standard“ for measuring natural killer’s function. However it is methodologically difficult for introduction in routine diagnostic practice. In our previous study, we showed a prognostic clinical significance of immune parameters when they are out of a optimal range (accentuated). In contrast, balanced “not accentuated” immune parameters associated with favorable clinical outcome. In this study, we attempted to explain the disparity of the accentuated but immunologically normal natural killer’s parameters that might serve as negative clinical prognostical biomarkers indicative of failed pregnancies. We have analyzed number natural killers %, their cytotoxicity, and their reciprocal correlation in 8,664 patients with reproductive failures. We found an elevated natural killer’s cytotoxicity in a significant part of infertility population. An elevated natural killer’s cytotoxicity was significantly more often registered in patient with multiple reproductive failures (41.6 %) detected in patients with uncomplicated infertility (18.7 %). In the entire clinical population, % of natural killers correlates with their cytotoxicity. Interestingly, we found this correlation was strongly dependent on status of natural killer’s levels. Natural killer’s % – natural killer’s cytotoxicity correlation was strongest (r = 0.2021, p < 0.0001) in patients’ group with high amount of natural killers % (> 17.5 %). Patients with amount of natural killers % between 15–17.5 % manifested lower but significant correlation of natural killer’s % – natural killer’s cytotoxicity (r = 0.1213, p = 0.0155). Additionally, a significant correlation (r = 0.2689, p < < 0.0001) between natural killer’s % and natural killer’s cytotoxicity was observed in patients group with natural killer’s levels of < 7 % (1.7–7.3 %). While, patient groups with natural killer’s % (7.3–15 %) did not demonstrate correlation of natural killer’s % – natural killer’s cytotoxicity. Consistent with our hypothesis, the “balanced zone” of natural killer’s % is tightly controlled and, thus, does not correlate directly with cytotoxicity. In contrast, the “accentuated zones” of natural killer’s % escape this control and directly affected cytotoxicity.
Keywords
Full Text:
PDFReferences
1. Beer A.E., Kwak J.Y., Ruiz J.E. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles. Am J Reprod Immunol, 1996; 35: 376-382. Crossref ● PubMed ● Google Scholar | ||||
| ||||
2. Bisset L.R., Lung T.L., Kaelin M., Ludwig E., Dubs R.W. Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland. Eur J Haematol, 2004; 72(3): 203-12. Crossref ● PubMed ● Google Scholar | ||||
| ||||
3. Chernyshov V.P., Sudoma I.O., Dons'koi B.V., Kostyuchyk A.A., Masliy Y.V. Elevated NK cell cytotoxicity, CD158a expression in NK cells and activated T lymphocytes in peripheral blood of women with IVF failures. Am J Reprod Immunol, 2010; 64: 58-67. Crossref ● PubMed ● Google Scholar | ||||
| ||||
4. Chernyshov V.P., Dons'koi B.V., Sudoma I.O., Goncharova Y.O. Favorable immune phenotype predicts successful implantation and pregnancy. Immunol Lett, 2014; 162(2 Pt B): 217-21. Crossref ● PubMed ● Google Scholar | ||||
| ||||
5. Chernyshov V.P., Dons'koi B.V., Sudoma I.O., Goncharova Y.O. Multiple immune deviations predictive for IVF failure as possible markers for IVIG therapy. Immunol Lett, 2016; 176: 44-50. Crossref ● PubMed ● Google Scholar | ||||
| ||||
6. Choi J., Lee S.J., Lee Y.A., Maeng H.G., Lee J.K., Kang Y.W. Reference values for peripheral blood lymphocyte subsets in a healthy korean population. Immune Netw, 2014; 14(6): 289-95. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
7. Chung H.J., Park C.J., Lim J.H., Jang S., Chi H.S., Im H.J., Seo J.J. Establishment of a reference interval for natural killer cell activity through flow cytometry and its clinical application in the diagnosis of hemophagocytic lymphohistiocytosis. Int J Lab Hematol, 2010; 32(2): 239-47. Crossref ● PubMed ● Google Scholar | ||||
| ||||
8. Coulam C.B., Goodman C. Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating C56+ cells. Early Pregnancy, 2000; 4(2): 90-8. PubMed ● Google Scholar | ||||
| ||||
9. Di Santo J.P. Natural killer cell developmental pathways: a question of balance. Annu Rev Immunol, 2006; 24: 257-286. Crossref ● PubMed ● Google Scholar | ||||
| ||||
10. Dons'koi B.V., Chernyshov V.P., Osypchuk D.V. Measurement of NK activity in whole blood by the CD69 up-regulation after co-incubation with K562, comparison with NK cytotoxicity assays and CD107a degranulation assay. J Immunol Methods, 2011; 30: 187-195. Crossref ● PubMed ● Google Scholar | ||||
| ||||
11. Donskoĭ B.V., Chernyshov V.P., Osypchuk D.V. The immunophenotypic characteristics of two functionally different natural killer cell subpopulations in peripheral human blood. Fiziol Zh, 2011; 57: 29-35. Crossref ● PubMed ● Google Scholar | ||||
| ||||
12. Dons'koĭ B.V., Chernyshov V.P., Sudoma I.O., Honcharova I.O., Osypchuk D.V. Qualitative analysis of accented CD158a receptor expression in NK-lymphocytes in women with reproductive failures. Lik Sprava, 2013; (1): 86-93. PubMed ● Google Scholar | ||||
| ||||
13. Dons'koi B.V., Chernyshov V.P., Sirenko V.Y., Strelko G.V., Osypchuk D.V. Immunobiology. Peripheral blood natural killer cells activation status determined by CD69 upregulation predicts implantation outcome in IVF. Immunobiology, 2014; 219: 167-71. Crossref ● PubMed ● Google Scholar | ||||
| ||||
14. Dons'koi B.V. Accentuated hypo- and hyper-NK lymphocyte CD8 expression is a marker of NK subsets' misbalance and is predictive for reproductive failures. Immunobiology, 2015; 220(5): 649-55. Crossref ● PubMed ● Google Scholar | ||||
| ||||
15. Golden-Mason L., Cox A.L., Randall J.A., Cheng L., Rosen H.R. Increased natural killer cell cytotoxicity and NKp30 expression protects against hepatitis C virus infection in high-risk individuals and inhibits replication in vitro. Hepatology, 2010; 52(5): 1581-9. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
16. Jentsch-Ullrich K., Koenigsmann M., Mohren M., Franke A. Lymphocyte subsets' reference ranges in an age- and gender-balanced population of 100 healthy adults - a monocentric German study. Clin Immunol, 2005; 116(2): 192-7. Crossref ● PubMed ● Google Scholar | ||||
| ||||
17. Kane K.L., Ashton F.A., Schmitz J.L., Folds J.D. Determination of natural killer cell function by flow cytometry. Clin Diagn Lab Immunol, 1996; 3(3): 295-300. PubMed ● PMC ● Google Scholar | ||||
| ||||
18. Karami N., Boroujerdnia M.G., Nikbakht R., Khodadadi A. Enhancement of peripheral blood CD56dim cell and NK cell cytotoxicity in women with recurrent spontaneous abortion or in vitro fertilization failure. J Reprod Immunol, 2012; 95(1-2): 87-92. Crossref ● PubMed ● Google Scholar | ||||
| ||||
19. Knorr D., Bachanova V., Michael RV., Miller J.S. Clinical utility of natural killer cells in cancer therapy and transplantation. Semin Immunol, 2014; 26: 161-172. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
20. Kutukculer N., Azarsiz E., Karaca N.E., Ulusoy E., Koturoglu G., Aksu G. A Clinical and Laboratory Approach to the Evaluation of Innate Immunity in Pediatric CVID Patients. Front Immunol, 2015; 27(6): 145. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
21. Lanier L.L. Natural killer cell receptor signaling. Curr Opin Immunol, 2003; 15: 308-14. Crossref ● Google Scholar | ||||
| ||||
22. Lee S.K., Na B.J., Kim J.Y., Hur S.E., Lee M., Gilman-Sachs A., Kwak-Kim J. Determination of clinical cellular immune markers in women with recurrent pregnancy loss. Am J Reprod Immunol, 2013; 70(5): 398-411. Crossref ● PubMed ● Google Scholar | ||||
| ||||
23. Le Bouteiller P., El Costa H., Aguerre-Girr M., Tabiasco J. Immunity of pregnancy: novel concepts. Bull Acad Natl Med, 2009; 193: 1029-1041. Crossref ● PubMed ● Google Scholar | ||||
| ||||
24. Matsubayashi H., Hosaka T., Sugiyama Y., Suzuki T., Arai T., Kondo A., Sugi T., Izumi S., Makino T. Increased natural killer-cell activity is associated with infertile women. Am J Reprod Immunol, 2001; 46: 318-322. Crossref ● PubMed ● Google Scholar | ||||
| ||||
25. Ogata K., An E., Shioi Y., Nakamura K., Luo S., Yokose N., Minami S., Dan K. Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol, 2001; 124(3): 392-7. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
26. Ogata K., Yokose N., Tamura H. Natural killer cells in the late decades of human life. Clin Immunol Immunopathol, 1997; 84: 269-75. Crossref ● PubMed ● Google Scholar | ||||
| ||||
27. Reichert T., DeBruyиre M., Deneys V., Tцtterman T., Lydyard P., Yuksel F., Chapel H., Jewell D., Van Hove L., Linden J. Lymphocyte subset reference ranges in adult Caucasians. Clin Immunol Immunopathol, 1991; 60(2): 190-208. Crossref ● PubMed ● Google Scholar | ||||
| ||||
28. Sansoni P., Cossarizza A., Brianti V. Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood, 1993; 82: 2767-73. Crossref ● PubMed ● Google Scholar | ||||
| ||||
29. Sun J.C., Lanier L.L. Natural killer cells remember: An evolutionary bridge between innate and adaptive immunity? Eur J Immunol, 2009; 39: 2059-2064. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
30. Sun C., Sun H.Y., Xiao W.H., Zhang C., Tian Z.G. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy. Acta Pharmacol Sin, 2015, 36(10):1191-9. Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
31. Thum M.Y., Bhaskaran S., Abdalla H.I., Ford B., Sumar N., Shehata H., Bansal A.S. An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome. Hum Reprod, 2004; 19(10): 2395-400. Crossref ● PubMed ● Google Scholar | ||||
| ||||
32. Thum M.Y., Bhaskaran S., Bansal A.S., Shehata H., Ford B., Sumar N., Abdalla H.I. Simple enumerations of peripheral blood natural killer (CD56+ NK) cells, B cells and T cells have no predictive value in IVF treatment outcome. Hum Reprod, 2005; 20(5): 1272-6. Crossref ● PubMed ● Google Scholar | ||||
| ||||
33. Torres A.J., Cisneiros P., Guedes R., Grassi M.F., Meyer R., Bendicho M.T., Lopes T.G., Félix G., Netto E.M., Brites C., Abe-Sandes K., Brandão C., Alcantara-Neves N., Freire S.M. Lymphocyte subset reference intervals in blood donors from northeastern. Brazil An Acad Bras Cienc, 2015; 87(2): 1019-25. Crossref ● PubMed ● Google Scholar | ||||
| ||||
34. Whiteside T.L., Herberman R.B. Role of human natural killer cells in health and disease. Clin Diagn Lab Immunol, 1994; 1: 125-33. PubMed ● Google Scholar | ||||
| ||||
35. Winger E.E., Reed J.L., Ashoush S., El-Toukhy T., Ahuja S., Taranissi M. Elevated Preconception CD56+16+ and/or Th1:Th2 Levels Predict Benefit from IVIG Therapy in Subfertile Women Undergoing IVF. Am J Reprod Immunol, 2011; 66: 394-403. Crossref ● PubMed ● Google Scholar |
Refbacks
- There are currently no refbacks.
Copyright (c) 2019 Studia biologica
This work is licensed under a Creative Commons Attribution 4.0 International License.