Prednisone increases apoptosis inin vitroactivated human peripheral blood T lymphocytes

Abstract

SUMMARYGlucocorticoid hormones (GCH) regulate, through the apoptotic process, the negative selection of immature T cells in the thymus. Because apoptosis seems to occur also in the maintenance of peripheral tolerance, we have investigated whether GCH may induce apoptosis in human mature lymphocytes. Peripheral blood lymphocytes (PBL) or peripheral CD4+ and CD8+ T cell subsets were cultured in the presence of phytohaemaglutinin (PHA) or PHA and prednisone (PDN) at 10-3-10-'2~ concentrations for 72, 96 and 120h. Cell cycle and membrane antigen expression were evaluated by flow cytometry and DNA degradation was detected by agarose gel electrophoresis. PDN blocks PBL growth in the GI phase of cell cycle and inhibits both IL-2 receptor (IL-2R) expression and IL-2 secretion. Apoptosis is clearly increased by PDN in PHA-activated human PBL, and the apoptotic effect of PDN is stronger on CD8+ than on CD4+ T lymphocytes.All these effects are dose-and time-dependent. The addition of exogenous IL-2 did not rescue lymphocytes from PDN-increased apoptosis. These results show that PDN increases apoptosis in mature activated human peripheral blood lymphocytes, suggesting a possible role of GCH in the maintenance of immune tolerance at post-thymic level.

A flow cytometric assessment of the lymphocyte immunophenotypes in dogs naturally infected with Babesia rossi

“…This is in contrast to a reported decrease in circulating CD4 + and CD8 + T lymphocytes in healthy dogs receiving prednisone at a daily dosage of 2 mg/kg for 14 days (127). Prednisone has been reported to induce in vitro apoptosis of peripheral T lymphocytes in a time-and dose-dependent fashion (128). The lack of a glucocorticoid effect noted on the T lymphocytes and subsets in our study may reflect a delayed effect of glucocorticoids on these lymphocytes, or reflect that the dosage used was not adequate to induce a decrease in the circulating T lymphocytes.…”

Advancements on phenotypic and functional characterization of non–antigen-specific CD8+CD28− regulatory T cells

“…Data are representative of analyses performed on lymphocytes from 10 healthy donors. its pharmacologic range [13], to cell cultures did not alter either the efficiency of in vitro generation of CD8ϩCD28Ϫ Treg (Figure 4a) or the suppressive activity of already in vitro-generated CD8ϩCD28Ϫ Treg (Figure 4b). These data suggest a functional resistance of CD8ϩCD28Ϫ Treg to the metabolic actions of corticosteroids.…”

“…Corticosteroid drugs are highly used in the treatment of autoimmune diseases for their immunosuppressive effects [13,26]. However, sensitivity of Treg to corticosteroids would be therapeutically detrimental since it would exacerbate the impairment of regulatory cells already existing in such diseases.…”

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia

“…The use of corticosteroids is generally considered only when toxicities are refractory to anti-IL-6 therapy. Although the use of steroids did not show impairment of in terms of response rates and durability of response after CAR T-cell therapy [74], they are known for suppressing T-cell function and/or inducing Tcell apoptosis [75]. In a phase 2 trial (NCT02435849), there were no mortalities attributed to CRS with symptomatic improvement to therapy with tocilizumab (37%) and other supportive M a n u s c r i p t care measures.…”