The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group. In general, MP decreased production of proinflammatory factors (IFN-, IL-2, IL-17, IL-21 and TNF-) by TCR-activated CD3+CD45RO+ cells from healthy donors and RA, consistent with the overall immunosuppressive mechanism of GC action. The correlation between CD4+CD45RO+HLA-DR+CD95+ T-cell contents and parameters reflecting production of proinflammatory mediators (IL-17, IL-21 and TNF-) in RA patients indicates maintenance of the pro-inflammatory potential of this T-cell population exposed to GC action. We suggest that relative resistance of CD4+CD45RO+CD95+HLA-DR+ T-cells of RA patients to the suppressor effect of GC leads to maintenance and even enhancement in the functional capacities of autoreactive cells in the pathogenesis of RA.
Otseneno vliianie raznykh kontsentratsiĭ gliukokortikoida (GK) metilprednizolona (MP) na izmenenie chisla CD4+CD95+HLA-DR+ T-kletok i ikh sposobnost' produtsirovat' provospalitel'nye mediatory in vitro v kul'turakh TCR-stimulirovannykh CD3+CD45RO+ T-limfotsitov. T-kletki poluchali ot zdorovykh donorov i bol'nykh revmatoidnym artritom (RA). Na fone TCR-aktivatsii MP povyshal chislo CD4+HLA-DR+CD95+ kletok v SD3+CD45RO+ kul'turakh, poluchennykh ot bol'nykh RA, i ne izmenial ikh soderzhanie u kontrol'noĭ gruppy. V tselom éffekty MP privodili k snizheniiu produktsii provospalitel'nykh faktorov (IFN-, IL-2, IL-17, IL-21 i TNF-) TCR-aktivirovannymi CD3+CD45RO+ kletkami zdorovykh donorov i bol'nykh RA, podtverzhdaia obshchiĭ immunosupressornyĭ mekhanizm deĭstviia GK. Vyiavlennye nami korreliatsii mezhdu soderzhaniem CD4+CD45RO+HLA-DR+CD95+ T-kletok s pokazateliami, otrazhaiushchimi produktsiiu provospalitel'nykh mediatorov (IL-17, IL-21 i TNF-) u bol'nykh RA, svidetel'stvuiut o sokhranenii provospalitel'nogo potentsiala étoĭ populiatsii T-kletok na fone deĭstviia GK. My polagaem, chto otnositel'naia rezistentnost' CD4+CD45RO+CD95+HLA-DR+ T-kletok bol'nykh RA k supressornomu deĭstviiu GK privodit k sokhraneniiu i usileniiu funktsional'nykh vozmozhnosteĭ autoreaktivnykh kletok v patogeneze RA.
Keywords: CD95; HLA-DR; glucocorticoid hormones; memory T cell; rheumatoid arthritis.