Dynamics of T-lymphocyte subpopulations’ recovery after influence of various damaging agents
AbstractIntroduction. Various damaging agents have different immunosuppressive effect on the immune system and cause pathogenetically varied reparative changes in it. Studying the mechanisms of T-cell recovery is important both for understanding the pathogenesis of reparative processes and for finding adequate methods for their correction.
Aim - to study the role of thymus and peripheral lymphoid organs (for example, the spleen) in the T-lymphocyte restoration after equal damage by cytostatic cyclophosphamide or sublethal irradiation.
Material and methods. C57BL/6 mice were divided into 3 groups. Group 1 (20 mice) received with cyclophosphamide once, group 2 (20 mice) was irradiated with X-rays (4 Gy) once, and group 3 (8 mice) was used as control. Mice were euthanized on days 10, 20, 30 and 60. The cellularity and subpopulations of T-cells in thymus and spleen were determined by flow cytometry.
Results. We have shown that radiation damages actively dividing thymocytes more deeply than cyclophosphamide. Some block is formed in the thymus at the stage of DN4 thymocytes, and complete recovery of cytotoxic T-cells in the spleen is not observed even by two months after sublethal irradiation. Radiation is more damaging to the CTL subpopulation, and CTLs are not completely restored either in the thymus or in the periphery by day 60. Actively dividing thymocytes are more susceptible to the action of damaging factors than mature splenocytes. Homeostatic proliferation with the conversion of the phenotype of naive T cells into central memory T-cells makes a significant contribution to the regenerative processes.
Conclusion. T-cells are more sensitive to ionizing radiation than to the action of cytostatics. And irradiation significantly damages not only the lymphoid elements, but also the thymic stroma. Both types of exposure lead to a decrease in the number of naive T-cells and the accumulation of surrogate memory T-cells, which should result in a narrowing of the T-cell receptor repertoire, the development of immunodeficiency and immunopathology associated with the T-cell response. We should understand it when prescribing the optimal corrective treatment after radiation and chemotherapy.
Keywords:T-lymphocytes; cyclophosphamide; X-ray; recovery; flow cytofluorimetry
For citation: Grinko E.K., Verigo K.S., Mukhina E.A., Sharova N.I., Komogorova V.V., Litvina M.M., Marzanova S.N., Donetskova A.D., Mitin A.N. Dynamics of T-lymphocytes regeneration after lymphopenia induction by cyclophosphane. Immunologiya. 2021; 42 (4): 346-55. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-346-355 (in Russian)
Funding. The study was carried out within the framework of the state task of the NRC Institute of Immunology FMBA of Russia (№ 22.005.16.800).
Conflict of interests. The authors declare no conflict of interests.
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