Regulatory and effector T-cells are differentially modulated by Dexamethasone

Downregulation of myeloma-induced ICOS-L and regulatory T cell generation by lenalidomide and dexamethasone therapy

“…In vitro, evidence exists for a lympholytic effect on HMCLs as well as altered autocrine production of key cytokines including TGF-b and IL-6, inducing growth arrest [45,46]. The impact of dexamethasone on immune regulatory and effector cells has been described [20]. The data presented in the current study demonstrate the differential effect of dexamethasone on T Reg and T Eff cell apoptosis, which together with lenalidomide-induced ICOSL gene down-regulation and the resulting reduction in T Reg cell generation, establish immunological synergy for the first time in the myeloma therapeutic setting.…”

“…An impact of dexamethasone on the adaptive and innate immune systems, including regulatory cells, has been documented [20] and we sought to examine the impact on tT Reg cell generation in our in vitro model system. Healthy donor CD4 + T cells were isolated and cultured with increasing doses of dexamethasone (0.1 lM, 1 lM, and 10 lM) or medium alone and then examined by FACS to determine the impact on apoptosis of both CD4 + CD25 + FoxP3 + T Reg cells and CD4 + CD25 + FoxP3 À T Eff cells.…”

Dose-dependent effects of dexamethasone on functional activity of T-lymphocytes with different grades of differentiation

“…Previously, it was believed that medullary thymocytes and peripheral lymphocytes are resistant to glucocorticoids. However, a recent study demonstrated, that certain subpopulations of mature T lymphocytes (effector of T cells, NK cells) undergo apoptosis under the action of glucocorticoids [10][11][12].…”

Cellular reactions of CD3+ CD4+ CD45RO+ T-lymphocytes on dexamethason in in normal patients and in patients with with rheumatoid arthritis in vitro

“…3). Результаты опубликованных исследований свидетельствуют об ингибирующем ýффекте ГК на продукцию IFNγ стимулированны-ми Тh1-лимфоцитами человека [11], предполагае-мым механизмом которого может быть непрямая трансрепрессия [16,24,34,36], реализуемая че-рез белок-белковые взаимодействия ГКР с транс-крипционными факторами (АР-1/CREB/ATF). Установлено, что фармакологические дозы ГК, подавляя активность Т-bet зависимого фактора STAT4, снижают синтез и секрецию IFNγ [8,36].…”

“…ГК ока-зывают комплексное воздействие на компонен-ты иммунной системы, в частности регулируют процессы клеточного гомеостаза Т-лимфоцитов [9][10][11]. Несмотря на широкое применение ГК, ис-следований, посвященных их влиянию на функ-циональную активность аутореактивных CD4 + Т-клеток, недостаточно, чтобы интерпретировать позитивные и негативные ýффекты гормонально-го лечения ýтой патологии.…”