Ukrainian Journal of Perinatology and Pediatrics. 2022. 2(90): 5-11; doi 10.15574/PP.2022.90.5
Tumanova L. E.¹, Kolomiіets E. V.¹, Rjabenko O. P.^2
1SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv
²Reproductive Clinic "Nadia", Kyiv, Ukraine

For citation: Tumanova LE, Kolomiіets EV. (2022). Features of CD3 +- and CD3+CD4 +-peripheral blood cells at different pregnancy stages in women with anamnese infertility. Ukrainian Journal of Perinatology and Pediatrics. 2(90): 5-11; doi 10.15574/PP.2022.90.5.
Article received: Jan 27, 2022. Accepted for publication: Apr 28, 2022.

Infertile marriage is a complex socio-economic problem; the frequency of infertility in Ukraine is 17-20%, which prompts further study of its mechanisms, including immune ones, in order to develop appropriate methods of correction.
Purpose – to characterize the phenotypic features of T-cells and their subpopulation of T-helpers (CD3+CD4+) with the expression of intracellular cytokines in women with a history of infertility at different stages of pregnancy.
Materials and methods. Relative levels of immunocompetent cells (cl) of blood, including intracellular expression of cytokines CD3+CD4+cells, in 436 non-pregnant (the reference group n) and 514 pregnant women with infertility at the first trimester and the second trimester of pregnancy were determined using a cellular cytofluorimeter and the corresponding test systems. Characteristics of indicators in pregnant women at the different terms in groups were analyzed: a – 4-7 weeks (140 women); b – 8-9 weeks (163 women); c – 10-12 weeks (133 women); d – 13-18 weeks (63 women); e – 19-28 weeks (15 women) compared to the group n and among themselves.
Results. The first 12 weeks of pregnancy in women with a history of infertility are characterized by high blood levels of T-helpers (CD3+CD4+-cl), and their activation according to the expression of markers CD25 and HLA-DR, and for 18 weeks – intracellular secretion of pro-inflammatory cytokines IFN-γ + and TNF-α, high expression of anti-inflammatory IL-4 was observed throughout the 27 weeks of follow-up.
The percentage of women with high levels in the blood of CD3+CD4+IFN-γ+- and CD3+CD4+TNF-α+-L is the highest during the first 12 weeks, from 13^th week these indicators for TNF-α, and with 20^th – for IFN-γ do not differ from non-pregnant ones. Since the beginning of pregnancy, the relative number of women with low expression of IL-4 and IL-10 T-helpers has significantly decreased; within 13-18 weeks, the percentage of such pregnant women is significantly increased to the reference group, and such women are the most vulnerable due to the possible weak reaction of the anti-inflammatory link to the state of tolerance.
Conclusions. The characteristics of peripheral blood immune system cell levels according to their CD phenotypes and intracellular cytokine expression indicate their participation in pregnancy mechanisms at different stages and individual analysis allows for negative predictions and improvement of pregnancy course in women with a history of infertility.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution.
The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: CD-phenotype of immunocompetent cells, intracellular cytokines, pregnant women, history of infertility.
REFERENCES

1. Arslan E, Colakoğlu M, Celik C, Gezginc K, Acar A, Capar M, Akoz M, Akyurek C. (2004). Serum TNF-alpha, IL-6, lupus anticoagulantand anticardiolipin antibody in women with and without a past history of recurrent miscarriage. Arch Gynec Obstet. 4 (270): 227-229. https://doi.org/10.1007/s00404-003-0547-0; PMid:15449074

2. Barkovskiy DE. (2019). Izmeneniya T-helper-assotsiirovannyih tsitokinov pri ugroze nevyinashivaniya beremennosti. Zaporozhskiy meditsinskiy zhurnal. 3: 169-191. doi: 10.14739/2310-1210.2019.

3. Bulmer JN, Williams PJ, Lash GE. (2010). Immune Cells in the Placental Bed. Int J Dev Biol. 54: 281-294. https://doi.org/10.1387/ijdb.082763jb; PMid:19876837

4. Chaouat G, Ledee-Bataille N, Dubanchet S. (2004). Th1/Th2 paradigm in pregnancy: paradigm lost? Cytokines pregnancy/early abortion:reexaming the Th1/Th2 paradigm. Int. Arch. Allergy Immunol. 13: 93-119. https://doi.org/10.1159/000074300; PMid:15153791

5. Chernobay LV, Tischenko AN, Lazurenko VV i dr. (2016). Rol narusheniya tsitokinovogo profilya v snizhenii fertilnosti. MIzhnarodniy medichniy zhurnal. 2: 38-43. URL: http://dspace.nbuv.gov.ua/bitstream/ handle/123456789/114004/08-Chernobai.pdf?sequence=1.

6. Hellberg S, Raffetseder J, Rundquist O, Magnusson R. (2021). Progesterone Dampens Immune Responses in In Vitro Activated CD4+T Cells and Affects Genes Associated With Autoimmune Diseases That Improve During Pregnancy. Front. Immunol. https://doi.org/10.3389/fimmu.2021.672168; PMid:34054852 PMCid:PMC8149943

7. Krukier II, Levkovich MA, Mihelson AF i dr. (2019). Vliyanie disbalansa tsitokinov okoloplodnyih vod i syivorotki krovi zhenschinyi na razvitie prezhdevremennyih rodov. Doktor Ru. 4 (159): 19-22. https://doi.org/10.31550/1727-2378-2019-159-4-19-22

8. Levkovich MA, Nefedova DD, Tsaturyan LD, Berdichevskaya YeM. (2016). Immunologicheskiye aspekty problemy nevynashivaniya beremennosti. Sovrem. probl. nauki i obrazovaniya. 3: 186.

9. Lissauer D, Eldershaw S, Inman Ch et al. (2015). Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile. Eur J Immunol. 45: 2858-2872. https://doi.org/10.1002/eji.201445404; PMid:26249148 PMCid:PMC4833190

10. Liu F, Guo J, Tian T, Wang H, Dong F, Huang H, Dong M. (2011). Placental trophoblasts shifted Th1/Th2 balance toward Th2 and inhibited Th17 immunity at fetomaternal interface. APMIS. 119: 597-604. https://doi.org/10.1111/j.1600-0463.2011.02774.x; PMid:21851417

11. Makarkov AI, Buyanova SN, Ivanova OG, Linnik AP. (2012). Osobennosti T-kletochnoy immunoregulyatsii pri nevyinashivanii beremennosti: evolyutsiya paradigmyi. Rossiyskiy vestnik akushera-ginekologa. 5: 10-16. URL: https://www.mediasphera.ru/issues/rossijskij-vestnik-akushera-ginekologa/2013/2/downloads/ru/031726-6122201321.

12. Moskalev AV, Gumilevskiy BYu, Apchel AV, Tsyigan VN. (2019). T-limfotsityi – «tsenzornyie» kletki immunnoy sistemyi. Vestnik rossiyskoy voenno-meditsinskoy akademii. 2 (21): 191-197. https://doi.org/10.17816/brmma25943

13. Sallusto F. (2016). Heterogeneity of Human CD4(+) T Cells Against Microbes. Annu Rev Immunol. 34: 317-334. https://doi.org/10.1146/annurev-immunol-032414-112056; PMid:27168241

14. Veropotvelyan PN, Veropotvelyan NP, Guzhevskaya IV. (2013). Tsitokinyi v sisteme mat-platsenta-plod pri fiziologicheskom i patologicheskom techenii beremennosti. Zdorove zhenschinyi. 1 (77): 126-129.

15. Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J. (2020). T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front. Immunol. https://doi.org/10.3389/fimmu.2020.02025; PMid:32973809 PMCid:PMC7461801

16. Yuzko OM, Yuzko TA, Rudenko NH. (2013). Stan ta perspektyvy vykorystannia dopomizhnykh reproduktyvnykh tekhnolohii pry likuvanni bezpliddia v Ukraini. Helth of women. 8: 26-30. URL: http://nbuv.gov.ua/UJRN/Zdzh_2013_8_8.