Deficient IL-10 Secretion by Dendritic Cells (DCs) and Activated Lymphocytes in Aplastic Anemia (AA) Patients.

Abstract

Background: Immunoregulatory cytokines (IL-10 and IL-12) secreted by the activated DCs and lymphocytes (LCs) mediate Th1 and Th2 immune response, respectively. Characteristic increase in Th1/Th2 ratio in AA patients might be responsible for autoreactive T-cell mediated suppression of hematopoiesis. However, functional characteristics of DCs initiating the Th1/Th2 disbalance in AA patients remain unelucidated. Aims: To study the functional characteristics of DCs and activated LCs in AA patients. Methods: We have carried out the flow cytometry analysis of the expression of costimulatory molecules by DCs generated from peripheral blood mononuclear cells (PBMC) of 13 AA patients before and after the immunosuppressive therapy (IST). DCs from 4 healthy donors (HD) were studied as a control group. Supernatants (SNs) of LPS activated DC cultures and LC cultures with or without PHA stimulation were studied for IL-10 production by ELISA. CD4+CD25+ regulatory T cell population of AA patients and HDs has being evaluated by means of magnetic beads for the negative selection of CD4+ T cells and immunofluorescence staining with anti-CD25 monoclonal antibodies. Results: DCs of 53,4% (7/13) of AA patients exhibited lower than HDs' DCs expression of CD83 - marker of mature DCs. Level of IL-10 production by DCs from AA patients was significantly lower compared with HDs; opposite to HDs' LCs, unstimulated LCs from 88,8% (16/18) of untreated AA patients failed to produce IL-10, however, LPS stimulation resulted in IL-10 secretion though to significantly lower levels compared with HDs; IST enhanced IL-10 production by DCs as well as stimulated and unstimulated LCs from AA patients, though to lower amounts than those of HDs. Few experiments in AA patients after long-term successful IST showed that DCs of AA patients with complete remission tend to produce even more IL-10 than those of HDs. Conclusion: Altered expression of CD83 by the DC from AA patients might influence the activation of cytotoxic T-cells. IL-10 downregulation might inhibit the generation of CD4+CD25+ regulatory T cell population and consequently, contribute to the expansion of cytotoxic T-cells and to the development of AA.