Medical Radiology and Radiation Safety. 2024. Vol. 69. № 5
DOI:10.33266/1024-6177-2024-69-5-66-74
E.A. Kodintseva1, A.А. Akleyev2
Prospects and Methods for Studying the Proliferative Capacity
of the Human Peripheral Blood Lymphocyte Subpopulations in Radiation Medicine
1 Urals Research Center for Radiation Medicine, Chelyabinsk, Russia
1 Southern-Urals State Medical University, Chelyabinsk, Russia
Contact person: E.A. Kodintseva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
CONTENT
Introduction
1. Proliferation of peripheral blood lymphocytes as an integrative indicator of the functional activity of ICS in normal and pathological conditions.
2. Features of proliferative activity of peripheral blood lymphocytes under the action of AI.
3. Methodological approaches to the quantitative determination of proliferating cells in human peripheral blood lymphocyte subpopulations.
Conclusion
Keywords: chronic radiation exposure, the Techa River, peripheral blood lymphocytes, proliferative activity, individual radiosensiti-
vity, late effects of radiation exposure
For citation: Kodintseva EA, Akleyev AА. Prospects and Methods for Studying the Proliferative Capacity of the Human Peripheral Blood Lymphocyte Subpopulations in Radiation Medicine. Medical Radiology and Radiation Safety. 2024;69(5):66–74. (In Russian). DOI:10.33266/1024-6177-2024-69-5-66-74
References
1. Akleyev AA. Immune Status of a Man Long after Chronic Radiation Exposure. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2020;65(4):29-35 (In Russ.). DOI: 10.12737/1024-6177-2020-65-4-29-35.
2. Akleyev AV, Varfolomeyeva TA. Sostoyanie Gemopoeza u Zhiteley Pribrezhnykh Sel Reki Techi = Status of Hematopoiesis in Residents of the Techa Riverside Villages. Consequences of Radioactive Contamination of the Techa River. Ed. A.V.Akleyev. Chelyabinsk, Kniga Publ., 2016. Р. 166-194 (In Russ.). DOI: 10.7868/ S0869803117020060.
3. Krestinina LYu, Silkin SS, Mikryukova LD, Epifanova SB, Akleyev AV. Solid Cancer Incidence Risk in the Ural Cohort of the Аccidentally Exposed Population: 1956–2017. Radiatsionnaya Gigiyena = Radiation Hygiene. 2020;13(3):6-17 (In Russ.). DOI: 10.21514/1998-426X-2020-13-3-6-17.
4. Boulton F. Ionising Radiation and Childhood Leukaemia Revisited. Medicine, Conflict, and Survival. 2019;35(2):144-170. DOI: 10.1080/13623699.2019.1571684.
5. Grant EJ, Brenner A, Sugiyama H, Sakata R, Sadakane A, Utada M, Cahoon EK, Milder CM, Soda M, Cullings HM, Preston DL, Mabuchi K, Ozasa K. Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009. Radiation Research. 2017;187(5):513-537. DOI: 10.1667/RR14492.1.
6. Ivanov VK, Kashcheev VV, Chekin SYu, Maksyutov MA, Tumanov KA, Kochergina EV, Lashkova OE, Menyailo AN, Karpenko SV, Lovachev SS, Korelo AM, Vlasov OK, Shchukina NV, Ivanov SA, Kaprin AD. Assessment of Radiation Risks of Malignant Neoplasms among the Population of Russian Regions Contaminated with Radionuclides as a Result of the Chernobyl Accident. Radiatsiya i Risk = Radiation and Risk. 2021;30(1):131-146 (In Russ.). DOI: 10.21870/0131-3878-2021-30-1-131-146.
7. Zhuntova GV, Azizova TV, Grigoryeva ES. Risk of stomach cancer incidence in a cohort of Mayak PA workers occupationally exposed to ionizing radiation. PLoS ONE 2020;15(4):e0231531. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231531. (Accessed 30 April 2024). DOI: 10.1371/journal.pone.0231531.
8. Krestinina LYu, Silkin SS, Degteva MO, Akleyev AV. Risk Analysis of the Mortality from the Diseases of the Circulatory System in the Ural Cohort of Emergency-Irradiated Population for the Years 1950–2015. Radiatsionnaya Gigiyena = Radiation Hygiene. 2019;12(1):52-61 (In Russ.). DOI: 10.21514/1998-426X-2019-12-1-52-61.
9. Tang FR, Loganovsky K. Low Dose or Low Dose Rate Ionizing Radiation-Induced Health Effect in the Human. Journal of Environmental Radioactivity. 2018;192:32-47. DOI: 10.1016/j.jenvrad.2018.05.018.
10. Sources, Effects and Risks of Ionizing Radiation. United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2020/2021. Report to the General Assembly, with Scientific Annexes. New York, United Nations, 2021. 244 р.
11. Al Fares E, Sanikidze T, Kalmakhelidze S, Topuria D, Mansi L, Kitson S, Molazadeh M. The Alleviating Effect of Herniarin Against Ionizing Radiation-Induced Genotoxicity and Cytotoxicity in Human Peripheral Blood Lymphocytes. Current Radiopharmaceuticals. 2022;15(2):141-147. DOI: 10.2174/1874471014666211012104808.
12. Lumniczky K, Impens N, Armengol G, Candéias S, Georgakilas AG, Hornhardt S, Martin OA, Rödel F, Schaue D. Low dose ionizing radiation effects on the immune system. Environment International. 2021;149:106212. Available at: https:// www.sciencedirect.com/science/article/abs/pii/S0265931X1830362X?via%3Dihub. Accessed 30 April 2024. DOI: 10.1016/j.envint.2020.106212.
13. Beauford SS, Kumari A, Garnett-Benson C. Ionizing Radiation Modulates the Phenotype and Function of Human CD4+ Induced Regulatory T Cells. BMC Immunology. 2020;21:18. Available at: https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-020-00349-w#article-info. (Accessed 30 April 2024). DOI: 10.1186/s12865-020-00349-w.
14. Burrack AL, Martinov T, Fife BT. T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes. Frontiers in Endocrinology. 2017;8:343. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723426/ Accessed 30 April 2024. DOI: 10.3389/fendo.2017.00343.
15. Manina IV, Sergeev VYu, Golubtsova NV, Sergeev АYu. Lymphocytes Blast-Transformation Reaction: Modification for Allergological Practice. Rossiyskiy Bioterapevticheskiy Zhurnal = Russian Journal of Biotherapy. 2018;17(2):88-92 (In Russ.). DOI: 10.17650/1726-9784-2018-17-2-88-92.
16. Moro-García MA, Mayo JC, Sainz RM, Alonso-Arias R. Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes. Frontiers in Immunology. 2018;9:339. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839096/ Accessed 30 April 2024. DOI: 10.3389/fimmu.2018.00339.
17. Han B, Dong L, Zhou J, Yang Y, Guo J, Xuan Q, Gao K, Xu Z, Lei W, Wang J, Zhang Q. The Сlinical Implication of Soluble PD-L1 (sPD-L1) in Patients with Breast Cancer and its Biological Function in Regulating the Function of T Lymphocyte. Cancer Immunology, Immunotherapy. 2021;70:2893-2909. DOI: 10.1007/s00262-021-02898-4.
18. Sokolova AS, Akhmadullina YR. Evaluation of the Proliferation Kinetics of PHA-Stimulated Lymphocytes of Chronically Exposed Individuals. Vestnik Soveta Molodykh Uchenykh i Spetsialistov Chelyabinskoy Oblasti = Bulletin of the Council of Young Scientists and Specialists of the Chelyabinsk Region. 2016;5(4-15):46-49. (In Russ.).
19. Zhou Y, Leng X, Mo C, Zou Q, Liu Y, Wang Y. The P53 Effector Perp Mediates the Persistence of CD4+ Effector Memory T Cell Undergoing Lymphopenia-Induced Proliferation. Immunology Letters. 2020;(224):14-20. DOI: 10.1016/j.imlet.2020.05.001.
20. Ellestad KK, Anderson CC. Two Strikes and You’re Out? The Pathogenic Interplay of Coinhibitor Deficiency and Lymphopenia-Induced Proliferation. Journal of Immunology. 2017;198(7):2534-2541. DOI: https://doi.org/10.4049/jimmunol.1601884.
21. Kim HK, Waickman AT, Castro E, Flomerfelt FA, Hawk NV, Kapoor V, Telford WG, Gress RE. Distinct IL-7 Signaling in Recent Thymic Emigrants Versus Mature Naive T Cells Controls T Cell Homeostasis. European Journal of Immunology. 2016;46(7):1669-1680. DOI: 10.1002/eji.201546214.
22. Markwart R, Condotta SA, Requardt RP, Borken F, Schubert K, Weigel C, Bauer M, Griffith TS, Förster M, Brunkhorst FM, Badovinac VP, Rubio I. Immunosuppression After Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naive T Cells but no Enduring Cell-Autonomous Defects in T Cell Function. PLoS One. 2014;9(12):e115094. Available at: https:///www.ncbi.nlm.nih.gov/pmc/articles/PMC4277344/ (Accessed 30 April 2024). DOI: 10.1371/journal. pone.0115094.
23. Patrakeeva VP. Cytokine Regulation of Proliferative Activity of Peripheral Blood Cells. Ekologiya Cheloveka = Human Ecology. 2015;12:28-33. (In Russ.).
24. Raué HP, Beadling C, Haun J, Slifka MK. Cytokine-Mediated Programmed Proliferation of Virus-Specific CD8(+) Memory T Cells. Immunity. 2013;38(1):131-139. DOI: 10.1016/j.immuni.2012.09.019.
25. Saleeva DV, Rozhdestvenskiy LM, Raeva NF, Vorobyeva ES, Zasukhina GD. Mechanisms of Antitumor Activity of Low Doses of Radiation Associated with Activation of Cells’ Defense System. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2023;68(1):15–18. (In Russ.). DOI: 10.33266/1024-6177-2023-68-1-15-18.
26. Bertucci A, Wilkins RC, Lachapelle S, Turner HC, Brenner DJ, Garty G. Comparison of Isolated Lymphocyte and Whole Blood-Based CBMN Assays for Radiation Triage. Cytogenetic and Genome Research. 2024;163(3-4):110-120. DOI: 10.1159/000533488
27. Garty G, Royba E, Repin M, Shuryak I, Deoli N, Obaid R, Turner HC, Brenner DJ. Sex and Dose Rate Effects in Automated Cytogenetics. Radiation Protection Dosimetry. 2023;199(14):1495-1500. DOI: 10.1093/rpd/ncac286.
28. Royba E, Repin M, Balajee AS, Shuryak I, Pampou S, Karan C, Wang YF, Lemus OD, Obaid R, Deoli N, Wuu CS, Brenner DJ, Garty G. Validation of a High-Throughput Dicentric Chromosome Assay Using Complex Radiation Exposures. Radiation Research. 2023;199(1):1-16. DOI: 10.1667/RADE-22-00007.1.
29. Herrera FG, Romero P, Coukos G. Lighting up the Tumor Fire with Low-Dose Irradiation. Trends in Immunology. 2022;43(3):173-179. DOI: 10.1016/j.it.2022.01.006.
30. Rusin M, Ghobrial N, Takacs E, Willey JS, Dean D. Changes in Ionizing Radiation Dose Rate Affect Cell Cycle Progression in Adipose Derived Stem Cells. PLoS One. 2021;16(4):e0250160. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078807/ (Accessed 30 April 2024). DOI: 10.1371/journal.pone.0250160.
31. Nikitina VA, Astrelina TA, Nugis VYu, Kobzeva IV, Lomonosova EE, Suchkova YuB, Malivanova TF, Brunchukov VA, Usupzhanova DYu, Brumberg VA, Rastorgueva AA, Dobrovolskaya EI, Karaseva TV, Kozlova MG, Pustovalova MV, Chigasova AK, Vorobyeva NYu, Osipov AN, Samoнlov AS. Cytogenetic Analysis of the Cell Line of Multipotent Human Mesenchymal Stromal Cells during Long-Term Cultivation after Exposure to X-Ray Radiation at Low and Medium Doses. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2023;68(1):5-14. (In Russ.). DOI: 10.33266/1024-6177-2023-68-1-5-14.
32. Palacio L, Goyer ML, Maggiorani D, Espinosa A, Villeneuve N, Bourbonnais S, Moquin-Beaudry G, Le O, Demaria M, Davalos AR, Decaluwe H, Beauséjour C. Restored Immune Cell Functions upon Clearance of Senescence in the Irradiated Splenic Environment. Aging Cell. 2019;18(4):e12971. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612633/ (Accessed 30 April 2024). DOI: 10.1111/acel.12971.
33. Khan AUH, Blimkie M, Yang DS, Serran M, Pack T, Wu J, Kang J-Y, Laakso H, Lee S-H, Le Y. Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice. nternational Journal of Molecular Sciences. 2021;22:7303. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC8306076/ (Accessed 30 April 2024). DOI: 10.3390/ijms22147303.
34. Sowemimo-Coker SO, Fast LD. Effects of Hypoxic Storage on the Efficacy of Gamma Irradiation in Abrogating Lymphocyte Proliferation and on the Quality of Gamma-Irradiated Red Blood Cells in Additive Solution 3. Transfusion. 2021;61(12):3443-3454. DOI: 10.1111/trf.16683.
35. Wang Q, Li S, Qiao S, Zheng Z, Duan X, Zhu X. Changes in T Lymphocyte Subsets in Different Tumors Before and After Radiotherapy: a Meta-analysis Frontiers in Immunology. 2021;12:648652. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242248/ (Accessed 30 April 2024). DOI: 10.3389/fimmu.2021.648652.
36. Busato F, Khouzai BE, Mognato M. Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art. International Journal of Molecular Sciences. 2022;23:10211. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499172/ (Accessed 30 April 2024). DOI: 10.3390/ijms231810211.
37. Duan WH, Jin LY, Cai ZC, Lim D, Feng ZH. 2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-Induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages. Biomedical and Environmental Sciences. 2021;34(9):693-704. DOI: 10.3967/bes2021.097.
38. Altukhova NA. Kliniko-Laboratornye Kriterii Uskoreniya Tempov Stareniya Uchastnikov Likvidatsii Posledstviy Avarii na ChAES = Clinical and Laboratory Criteria for Accelerating the Rate of Aging of Participants in the Liquidation of the Consequences of the Chernobyl Accident. Extended abstract of candidate’s thesis in Biol. St. Petersburg, 2005. 24 р. (In Russ.).
39. Markina TN, Akleyev AV, Veremeyeva GA. Proliferative Activity and Cell Cycle of Peripheral Blood Lymphocytes (PBL) at Late Time after Chronic Radiation Exposure in Man. Radiatsiya i Risk = Radiation and Risk. 2011;20(1):50-58. (In Russ.).
40. Akleyev AA, Blinova EA, Dolgushin II. Mitotic Activity of Lymphocytes and Immunological Status of Man at Later Time Points after Chronic Radiation Exposure. Immunologiya = Immunology. 2018;39(4):202-207. (In Russ.). DOI: 10.18821/0206-4952-2018-39-4-202-207.
41. Faivre L, Lecouflet L, Liu W-Q, Khadher I, Lahaie C, Vidal M, Legouvello S, Beaumont J-L, Bierling P, Rouard H, Birebent B. Quality Control of Extracorporeal Photochemotherapy: Proliferation Assay Using CFSE Validated According to ISO 15189:2007 Standards. Cytometry. Part B. 2015;88B:30-39. DOI: 10.1002/cytob.21188.
42. Elias G, Ogunjimi B, Van Tendeloo V. Tracking Dye-Independent Approach to Identify and Isolate in vitro Expanded T Cells. Cytometry. Part A. 2019;95(10):1096-1107. DOI: 10.1002/cyto.a.23867.
43. Frahm SO, Zott B, Dworeck C, Steinmann J, Neppert J, Parwaresch R. Improved ELISA Proliferation Assay (EPA) for the Detection of in Vitro Cell Proliferation by a New Ki-67-Antigen Directed Monoclonal Antibody (Ki-S3). Journal of Immunological Methods. 1998;211(1-2):43-50. DOI: 10.1016/s0022-1759(97)00175-0.
44. Bulycheva TI, Deyneko NL, Grigor’eva AA. The Immune Cytochemical Evaluation of Reaction of Phytohemagglutinin Stimulation of Lymphocytes with Monoclonal Antibodies Ki-67. Klinicheskaya Laboratornaya Diagnostika = Clinical Laboratory Diagnostics. 2014;59(7):51-54. (In Russ.).
45. Frahm SO, Rudolph P, Dworeck C, Zott B, Heidebrecht H, Steinmann J, Neppert J, Parwaresch R. Immunoenzymatic Detection of the New Proliferation Associated Protein P100 by Means of a Cellular ELISA: Specific Detection of Cells in Cell Cycle Phases S, G2 and M. Journal of Immunological Methods. 1999;223(2):147-153. DOI: 10.1016/s0022-1759(98)00217-8.
46. Malisheva MV, Moraleva AA, Deyneko NL, Bulycheva TI, Zatsepina OV. Comparative Analysis of the Expression of Key Nucleolar Proteins in Peripheral Blood Lymphocytes of Healthy Donors Activated for Proliferation in Vitro. Immunologiya = Immunology. 2010;31(1):13-17. (In Russ.).
47. Chulkina MM, Trofimov DYu, Kofiadi IA, Alekseev LP, Savilova AM. Comparative Аnalysis of Different Cytokines and Transcription Factors mRNA Expression in Lymphocytes Activated by ConA. Immunologiya = Immunology. 2014;35(6): 306-312. (In Russ.).
48. Vosoughi H, Azimian H, Khademi S, Rezaei AR, Najafi-Amiri M, Vaziri-Nezamdoost F, Bahreyni-Toossi MT. PHA Stimulation May Be Useful for FDXR Gene Expression-Based Biodosimetry. Iranian Journal of Basic Medical Sciences. 2020;(23):449-453. DOI: 10.22038/ijbms.2020.42350.9997.
49. Schüle S, Hackenbroch C, Beer M, Muhtadi R, Hermann C, Stewart S, Schwanke D, Ostheim P, Port M, Scherthan H, Abend M. Ex-Vivo Dose Response Characterization of the Recently Identified EDA2R Gene after Low Level Radiation Exposures and Comparison with FDXR Gene Expression and the γH2AX Focus Assay. International Journal of Radiation Biology. 2023;99(10):1584-1594. DOI: 10.1080/09553002.2023.2194402.
50. Kudryavtsev IV, Zurochka АV, Khaydukov SV, Chereshnev VA. Application of the Flow Cytometry Method to Assess the Proliferative Activity of Cells in Biomedical Research. Rossiyskiy Immunologicheskiy Zhurnal = Russian Journal of Immunology. 2012;6-14(3-1):21-40 (In Russ.).
51. Schwab L, Michel G, Bein G, Hackstein H. CD71 Surface Analysis of T Cells: a Simple Alternative for Extracorporeal Photopheresis Quality Control. Vox Sang. 2020;115(1):81-93. DOI: 10.1111/vox.12850.
52. Younes SA, Talla A, Pereira Ribeiro S, Saidakova EV, Korolevskaya LB, Shmagel KV, Shive CL, Freeman ML, Panigrahi S, Zweig S, Balderas R, Margolis L, Douek DC, Anthony DD, Pandiyan P, Cameron M, Sieg SF, Calabrese LH, Rodriguez B, Lederman MM. Cycling CD4+ T Сells in HIV Infected Immune Nonresponders Have Mitochondrial Dysfunction. Journal of Clinical Investigation. 2018;128(11):5083-5094. DOI: 10.1172/JCI120245.
53. Marchenko DM, Saydakova EV. Novel Рuman T Сell Proliferation Markers. Vestnik Permskogo Universiteta. Biologiya = Bulletin of Perm University. Series Biology. 2021;(4):316-323. (In Russ.). DOI: 10.17072/1994-9952-2021-4-316-323.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. This study was carried out within the framework of the state assignment of the FMBA of Russia: “Evaluation of the medical and biological effects of chronic radiation exposure and mechanisms of their development to improve the methods for early detection of exposure effects” (Immunohematopoiesis-24)”.
Contribution. All authors confirm that their authorship meets the international ICMJE criteria. Kodintseva Е. А. ‒ conceived and designed the study, prepared the first draft of the article, read and approved the final version before publication. Akleуev А. А. ‒ conceived and designed the study, scientific editing, read and approved the final version before publication.
Article received: 20.05.2024. Accepted for publication: 25.06.2024.