Oligoclonality And Subpopulation Structure Of Bone Marrow T-Cells In Patients With Aplastic Anaemia

Introduction. The main pathogenetic mechanism of the development of aplastic anemia (AA) is a violation of the immune regulation of hematopoiesis.Aim: to study of the subpopulation composition of T-cells and the repertoire of the T-cell receptor in AA patients.Patients and Methods. The study included AA patients (n = 40) without prior immunosuppressive therapy in 2018-2020. The T-cell subpopulation structure and T-cell receptor V beta-family (TCR-V beta) oligoclonality were studied in samples of bone marrow using flow cytometry.Results. We report characteristic properties of T-cell subpopulations of bone marrow in all AA patients: elevated counts of cytotoxic T-cells, effector CD4(+) and CD8(+) cells, CD4(+) memory cells, which may suggest a long-term antigenic stimulation with subsequent activation of these cell subpopulations resulting in hyperexpression of pro-inflammatory cytokines. Diminishing of naive CD4(+) and CD8(+) cells, regulatory and double negative T-cells may indicate a relaxing control of cytokine-producing T-cells. A relationship has been established between the AA severity and counts of effector, regulatory, double negative and PD-1 positive T-cells. A highest count of potentially cytokine-producing T-cells and lowest count of cells involved in T-cell activity regulation were observed in very severe AA patients. Studies of the TCR-V beta repertoire revealed oligoclonal expansion in the cytotoxic T-cell subpopulation.Conclusion. Enrichment in selected V beta families suggests autoreactive T-cell clonality and attests to the immune nature of AA. A dynamic TCR-V beta repertoire assay may be recommended in the disease monitoring. Flow cytometry helps identify valuable biomarkers for T-cell clone monitoring in AA and a better assessment of the disease progression.