INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Regulatory and Effector T-cells are Differentially Modulated by Dexamethasone
Autor/es:
PANDOLFI J; DELFINO L; BAZ P; FERNÁNDEZ P; ERCOLANO M; GAUNA A; FAINBOIM L; ARRUVITO L
Lugar:
Los Cocos. Córdoba
Reunión:
Congreso; LXI Reunión Científica Anual de la SAI.; 2013
Resumen:
# 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
effects 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 analyzed 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 0.5mg of 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 not 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.