DOI: https://doi.org/10.22263/2312-4156.2020.6.122
Zybleva S.V., Zyblev S.L.
Indicators of CD3-CD16+CD56+ and CD3+CD16+CD56+ lymphocytes with satisfactory primary kidney graft function
Republican Research Center for Radiation Medicine and Human Ecology, Gomel, Republic of Belarus
Vestnik VGMU. 2020;19(6):122-131.
Abstract.
Objectives. To study the dynamics of CD3-CD16+CD56+ and CD3+CD16+CD56+ lymphocytes in patients after kidney transplantation with satisfactory primary graft function.
Material and methods. 197 recipients underwent kidney transplantation. All patients were divided into 3 groups. The first group (PGF, n=101) consisted of patients with satisfactory primary graft function without rejection episodes, the second group (PGD, n=82) included patients with primary graft dysfunction without rejection episodes, the third group (GR, n=14) was composed of patients with primary graft dysfunction and graft rejection verified on the basis of renal transplant biopsy. A comparison group (CG) consisted of 90 healthy volunteers. Graft function was assessed according to the following criteria: primary graft function was characterized by creatinine level below 300 μmol/l on the 7th day after surgery; when creatinine concentration was equal to or higher than 300 μmol/l and (or) in case of need for dialysis during the first week after transplantation, the state was classified as kidney graft dysfunction. Immunological examination was carried out on the 1st, the 3rd, the 7th, the 30th and the 90th days after the transplantation. The level of CD3-CD16+CD56+ and CD3+CD16+CD56+ lymphocytes was determined.
Results. In the PGF group, a significant predominance of the absolute NK level from the 3rd day to the 30th day was revealed only in comparison with the GR group. The relative NK level was significantly higher in the PGF group compared to the GR group beginning with the 30th day. No correlation was found between the relative and absolute NK levels and creatinine levels throughout the study. There was a significant increase in the absolute and relative NKT level beginning with the 30th day in the PGF group compared to the PGD and GR groups. A negative correlation was found between the absolute NKT level and creatinine level on the 30th and the 90th days and the relative level of these lymphocytes with the creatinine level on the 90th day.
Conclusions. The results of the study can be used for the immunological monitoring in the early post-transplantation period.
Key words: CD3-CD16+CD56+ and CD3+CD16+CD56+, kidney transplantation.
References
1. Braun M, Müller B, ter Meer D, Raffegerst S, Simm B, Wilde S, et al. The CD6 scavenger receptor is differentially expressed on a CD56 natural killer cell subpopulation and contributes to natural killer-derived cytokine and chemokine secretion. J Innate Immun. 2011;3(4):420-34. doi: http://dx.doi.org/10.1159/000322720
2. Yu J, Mao HC, Wei M, Hughes T, Zhang J, Park I, et al. CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood. 2010 Jan;115(2):274-81. doi: http://dx.doi.org/10.1182/blood-2009-04-215491
3. Neudoerfl C, Mueller BJ, Blume C, Daemen K, Stevanovic-Meyer M, Keil J, et al. The Peripheral NK Cell Repertoire after Kidney Transplantation is Modulated by Different Immunosuppressive Drugs. Front Immunol. 2013 Feb;4:46. doi: http://dx.doi.org/10.3389/fimmu.2013.00046
4. Rajalingam R. The impact of HLA class I-specific killer cell immunoglobulinlike receptors on antibody-dependent natural killer cell-mediated cytotoxicity and organ allograft rejection. Front Immunol. 2016 Dec;7:585. doi: http://dx.doi.org/10.3389/fimmu.2016.00585
5. Hadad U, Martinez O, Krams SM. NK cells after transplantation: friend or foe. Immunol Res. 2014 May;58(2-3):259-67. doi: http://dx.doi.org/10.1007/s12026-014-8493-4
6. Laffont S, Cyril S, Ortaldo J, Coudert JD, Guéry J-C. Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells. Blood. 2008 Aug;112(3):661-71. doi: http://dx.doi.org/10.1182/blood-2007-10-120089
7. Godfrey DI, Kronenberg M. Going both ways: Immune regulation via CD Id-dependent NKT cells. J Clin Invest. 2004 Nov;114(10):1379-88. doi: http://dx.doi.org/10.1172/JCI23594
8. Lee PT, Putnam A, Benlagha K, Teyton L, Gottlieb PA, Bendelac A. Testing the NKT cell hypothesis of human IDDM pathogenesis. J Clin Invest. 2002 Sep;110(6):793-800. doi: http://dx.doi.org/10.1172/JCI15832
9. Dugast E, David G, Oger R, Danger R, Judor J-P, Gagne K, et al. Broad impairment of natural killer cells from operationally tolerant kidney transplanted patients. Front Immunol. 2017 Dec;8:1721. doi: http://dx.doi.org/10.3389/fimmu.2017.01721
10. Bromberg JS, Heeger PS, Li XC. Evolving paradigms that determine the fate of an allograft. Am J Transplant. 2010 May;10(5):1143-8. doi: http://dx.doi.org//10.1111/j.1600-6143.2010.03033.x
11. Sagoo P, Perucha E, Sawitzki B, Tomiuk S, Stephens DA, Miqueu P, et al. Development of a crossplatform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1848-61. doi: http://dx.doi.org/10.1172/JCI39922
12. Newell KA, Turka LA. Tolerance signatures in transplant recipients. Curr Opin Organ Transplant. 2015 Aug;20(4):400-5. doi: http://dx.doi.org/10.1097/MOT.0000000000000207
13. Trojan K, Zhu L, Aly M, Weimer R, Bulut N, Morath C, et al. Association of peripheral NK cell counts with Helios+ IFN-γ- Tregs in patients with good long-term renal allograft function. Clin Exp Immunol. 2017 Jun;188(3):467-479. doi: http://dx.doi.org/10.1111/cei.12945
14. Yu G, Xu X, Vu MD, Kilpatrick ED, Li XC. NK cells promote transplant tolerance by killing donor antigen-presenting cells. J Exp Med. 2006 Aug;203(8):1851-8. doi: http://dx.doi.org/10.1084/jem.20060603
15. Deniz G, Erten G, Can Kücüksezer U, Kocacik D, Karagiannidis C, Aktas E, et al. Regulatory NK cells suppress antigen-specific T cell responses. J Immunol. 2008 Jan;180(2):850-7. doi: http://dx.doi.org/10.4049/jimmunol.180.2.850
Information about authors:
Zybleva S.V. – Candidate of Medical Sciences, academic secretary, immunologist, Republican Research Center for Radiation Medicine and Human Ecology;
ORCID: https://orcid.org/0000-0003-3061-5324
Zyblev S.L. – Candidate of Medical Sciences, associate professor, surgeon of the surgical department (transplantation, reconstructive and endocrine surgery), Republican Research Center for Radiation Medicine and Human Ecology,
ORCID: https://orcid.org/0000-0002-0968-6630
Correspondence address: Republic of Belarus, 246000, Gomel, 5 Ilicha str., Republican Research Center for Radiation Medicine and Human Ecology, Scientific Department. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Svetlana V. Zybleva.
