Dynamics of T-lymphocytes regeneration after lymphopenia induction by cyclophosphane
Introduction. Chemotherapy drugs used in medicine, mainly for the treatment of cancer, belong to a group of factors that cause damage of the immune system. The study of the mechanisms of T-cell recovery after exposure to cytostatic agents is important both for understanding the pathogenesis of their damaging action and for finding the correct therapy. Aim of the study - to investigate the role of thymus and the peripheral lymphoid organs in T-cell restoration after exposure to cyclophosphamide in C57BL/6 mice. Material and methods. Cyclophosphamide was administered intraperitoneally to experimental animals once at a dose of 125 mg/kg. Mice were euthanized on days 0, 10, 20, 30, and 60 after cyclophosphamide administration. The total number of cells and the lymphocyte subpopulations in the thymus and spleen were determined by flow cytometry. Results. We found that actively dividing thymus cells are more defenseless to the action of the drug than spleen lymphocytes. At the same time, recovery processes in the thymus begin earlier (on day 20), followed by slow recovery of spleen lymphocytes (by day 60). However, complete regeneration of cytotoxic T-cells (CTLs) in the spleen is not observed even by 60 days. The study of the age phenotype of T-cell subpopulations showed that cyclophosphamide intensifies the phenomenon of the conversion of the naive T-cells into central memory T-cells. Conclusion. Cyclophosphamide has a heavy cytotoxic effect on the T cells of C57BL/6 mice, with predominant damage in highly dividing thymocyte populations. Thymopoiesis is unable to compensate for the deficiency of peripheral T-cell populations, which leads to an increase in homeostatic proliferation of T-cells, conversion of naive T-cell phenotype and the accumulation of T-helpers and CTLs with the phenotype of central memory T-cells. These changes can narrow the repertoire of T-cell receptors, lead to impaired immune surveillance and the possible growth of oncological, autoimmune and infectious diseases in the future.