Regulatory and effector T-cells are differentially modulated by Dexamethasone

JULIETA PANDOLFI; L DELFINO; PLÁCIDA BAZ; PABLO FERNANDEZ; M ERCOLANO; A GAUNA; LEONARDO FAINBOIM; LOURDES ARRUVITO

Los Cocos, Cordoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Background: It is assumed that the ratio between effector T cells (Teff) and regulatory T cells (Tregs) controls the immune reactivity within the CD4+ T-cell compartment. However, the immune state could be altered by immunomodulatory drugs, like Glucocorticoids (GC). Aims: 1) To study the in vitro Dexamethasone (Dex) effect on the frequency, sensitivity to apoptosis and functionality of Teff and Tregs, 2) To analyze the effect of intravenous pulses of Methylprednisolone (MP) on the frequency and function of Tregs and Teff in GC-treated-euthyroid patients with Graves Opthalmophathy (GO). Methodology and Results: Dex induced on Tregs a dose and time-dependent apoptosis which resulted in a relative increase of Teff. After TCR activation, Dex induced a strong proliferative inhibition on Teff, but a weaker proliferative inhibition on Tregs, and both effecs were restored by IL-2. The highest dose of IL-2 prevented apoptosis on all FOXP3+CD4+ T cells. Meanwhile, the lowest dose only rescued those cells with the higher CD25 expression. Finally, a short time exposure to Dex did not affect Tregs in vitro suppressor capacity. We also analized the FOXP3+CD4+ T cell frequency in two groups of GO patients treated with MP: group I (3 consecutive pulses of 1mg/day), and group II (1 weekly pulse of 0.5 mg MP/pulse). We found that MP induced a decrease frequency of Tregs only in the group 1. However, in both groups treatment with GC affected Teff function. Conclusion: During the course of an immune response, GC exerts differential effects on CD4+ T cells by inducing a strong inhibition of the proliferation of Teff, and a differential apoptosis of Tregs. Additionally, low doses or short time exposure to GC did no affect Tregs frequency. However, higher doses of GC induced raise levels of apoptosis on Tregs. This effect could be modulated by IL-2, which even in very low amount could impact on Tregs homeostasis.