The in vitro effect of dexamethasone on maturation and differentiation of CD4+CD45RO+ T-cells in rheumatoid arthritis

Abstract

Aim. To study the effect of dexamethasone (Dex) on activation and generation of terminally differentiated effector CD4+ T-lymphocytes (TEMRA) in cultured CD3+CD45RO+ T cells under the conditions mimicking stimulation of the T-cell receptor in vitro as it occurs in health and rheumatoid arthritis (RA). Methods. The study was performed on mononuclear leukocytes isolated from heparinized venous blood of 50 patients with rheumatoid arthritis. Changes in the T-lymphocyte immunophenotype were detected using flow cytofluorometry. Secretion of cytokine IL-2 by CD3+ CD45ROT+ cells was assessed by ELISA. Expression of hTERT, U2af1l4, and Gfi1 gene mRNA in CD3+CD45RO+ T cells was measured by polymerase chain reaction. Results. During the in vitro TCR activation of cultured CD3+CD45RO+ T cells, Dex participated to a variable extent in formation of a subpopulation of terminally differentiated effectors (CD3+CD4+CD45RO-CD28- TEMRA), which are characterized by low telomerase activity, loss of costimulation (CD28) and activation (CD25) molecules, and re-expression of the high molecular weight CD45-CD45RA receptor isoform both in healthy individuals and RA patients. Conclusion. The population of CD3+CD4+CD45RO-CD28- lymphocytes is a key participant in the pathogenesis of RA by accelerating their negative impact during the glucocorticoid therapy. This lymphocyte population contributes to RA progression particularly due to the powerful discharge of proinflammatory mediators.